KR20100123050A - Multiple snp markers, microarray and diagnosis kit for sasang constitution - Google Patents
Multiple snp markers, microarray and diagnosis kit for sasang constitution Download PDFInfo
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Abstract
Description
본 발명은 사상체질 진단용 다중 SNP(Single Nucleotide Polymorphism) 마커, 그를 포함하는 마이크로어레이, 및 그를 이용한 사상체질 진단용 키트에 관한 것이다.The present invention relates to a single Nucleotide Polymorphism (SNP) marker for filamentous constitution diagnosis, a microarray including the same, and a kit for filamentous constitution diagnosis using the same.
1894년 동무 이제마 선생에 의하여 창안된 사상의학은 사람의 체질을 태양, 소양, 태음 및 소음의 네 가지로 분류하고 각 체질에 대한 생리, 병리, 진단 감별법, 치료와 약물, 식품 섭취에 이르기까지 서로 연계를 갖고 이를 임상에 응용할 수 있는 새로운 방법을 제시하였으며(동의수세보원, 1984, 이제마), 현재, 한의학에서 중요한 임상적 방법으로 이용되고 있다. Founded in 1894 by Dr. Nesuma, ideology, he divided human constitutions into four categories: sun, cultivation, lunar and noise, and physiology, pathology, diagnostic differentiation, treatment, medication, and food intake. A new method of linking and applying it to the clinic has been proposed (Dong-Soo Suwon, 1984, Jeuma), and is currently used as an important clinical method in oriental medicine.
전통적으로 사상체질의 판별은 개인의 음성, 외모, 체형, 성격 및 다양한 외형적인 생물학적 지표를 종합적으로 이용하여 수행하여 왔으며, 숙련된 전문가에 의하여 주관적 판단을 바탕으로 진단이 행해지고 있다(조동욱 외, 사상의학회지 8권 12호, 1996). Traditionally, discrimination of Sasang Constitution has been performed by comprehensively using voice, appearance, body type, personality and various external biological indicators, and diagnosis is performed based on subjective judgment by skilled experts. Korean Journal of Medicine 8, 12, 1996).
한편, 동의수세보원에 의하면, 체질은 선천적이며 일생에 걸쳐서 변하지 않는다고 알려져 있으므로, 생물학적으로는 유전적인 특성이라고 할 수 있다. 사람의 모든 생물학적 형질은 유전자의 정보를 근간으로 발현되는 것이며, 따라서, 사상의학에서 제시하는 체질적 속성 역시 유전자가 지닌 형질에 내재되어 있는 속성이라 할 수 있다. On the other hand, according to the synod Suwon source, because the constitution is known to be innate and does not change throughout life, it can be said to be a biological characteristic. All biological traits in humans are expressed based on gene information, so the constitutional attributes suggested by ideology are also inherent in the traits of genes.
모든 생물의 유전체는 진화과정에서 자손들의 유전체에 변이(genomic variation)를 생기게 하는 자발적 돌연변이(mutation)를 겪는다(Gusella, Ann. Rev. Biochem. 55, 831-854, 1986). 유전체의 변이는 해당 생물종에게 있어서 진화적으로 이익 또는 불이익을 주거나 중성적일 수 있다. 기능적으로 매우 중요한 유전자의 변이의 경우, 치사적인 불이익을 주어 자손에게 전달되지 않는 경우도 있으며, 그렇지 않은 경우에는, 결국에는 종의 대부분에 DNA가 삽입되어 효과적으로 선조 형태가 되며, 다양한 생물학적 형질과 연관되어 종 집단 중에 서열의 다형성(polymorphism) 형태로 공존한다. 이러한 다형에는 RFLP(restriction fragment length polymorphism), STR(short tandem repeats) 및 SNP(single nucleotide polymorphism) 등이 알려져 있다. The genomes of all living organisms undergo spontaneous mutations that lead to genomic variations in their offspring during evolution (Gusella, Ann. Rev. Biochem. 55, 831-854, 1986). Mutations in the genome can be evolutionarily beneficial or disadvantageous or neutral to the species in question. In the case of functionally important gene mutations, there are cases in which lethal penalties are not transmitted to offspring; otherwise, DNA is inserted into most of the species, effectively leading to ancestral forms and associated with various biological traits. And coexist in the form of polymorphisms of sequence among species populations. Such polymorphisms include restriction fragment length polymorphism (RFLP), short tandem repeats (STR), and single nucleotide polymorphism (SNP).
이 중 SNP는 동일한 종의 개체 사이의 단일 뉴클레오티드(nucleotide) 변이이며, SNP가 단백질 암호화 영역에 발생하는 경우, 다형성 형태 중 어느 하나에 의 하여 결함 있거나 변이된 단백질이 발현될 수도 있다. 비코딩 영역에 SNP가 발생할 경우는 결함 있는 스플라이싱(splicing)의 결과로서 결함 있거나 변이된 단백질의 발현을 초래할 수도 있으며, 어떤 SNP는 표현형에 아무런 영향을 미치지 않을 수도 있다. 인간의 경우 약 1,000 bp 마다 1회의 빈도로 SNP가 발생하는 것으로 알려져 있으며, 이들 SNP가 질병과 같은 표현형에 영향을 미치는 경우, SNP를 포함하는 폴리뉴클레오티드(polynucleotide)는 이러한 질병이나 생물학적 표현 형질을 진단하기 위한 프라이머(primer) 또는 탐침(probe)으로 사용될 수 있다.Among them, SNPs are single nucleotide variations between individuals of the same species, and when SNPs occur in the protein coding region, defective or mutated proteins may be expressed by any of the polymorphic forms. The occurrence of SNPs in non-coding regions may result in the expression of defective or mutated proteins as a result of defective splicing, and some SNPs may have no effect on the phenotype. In humans, SNPs are known to occur once every 1,000 bp. When these SNPs affect phenotypes such as diseases, polynucleotides containing SNPs diagnose these diseases or biological expression traits. It can be used as a primer or a probe for the purpose.
상기한 바와 같이 전통적으로 행해져온 사상체질의 판별은 피검자의 음성, 외모, 체형, 성격을 포함하는 다양한 내외형적인 생물학적 지표를 종합하여 숙련된 전문가에 의하여 주관적 판단을 바탕으로 이루어지고 있다. 상기 체질 판별방법에 있어서, 생물학적 지표의 측정이 객관적이고 과학적인 방법을 통하여 정밀하게 이루어지지 않고 있으며, 측정된 지표의 값을 종합하여 최종 체질을 판별함에 있어서도 기준이 판정자의 주관에 의존하므로 판정된 체질의 정확성과 재현성에 심각한 문제가 존재한다. The discrimination of ideological constitution, which has been traditionally performed as described above, is based on subjective judgment by a skilled expert by combining various internal and external biological indicators including the voice, appearance, body shape, and personality of the subject. In the above constitution discrimination method, the measurement of biological indicators is not precisely made through an objective and scientific method, and the criteria are determined because the criteria are dependent on the subjectivity of the judge in determining the final constitution by combining the values of the measured indicators. There are serious problems with the accuracy and reproducibility of constitution.
사상체질의 판별을 용이하게 하기 위하여, 종래에는 손가락과 금이나 은가락지의 접촉 시의 신체 반응을 측정하거나(대한민국 등록특허 10-0455996, 대한민국 등록실용 20-0325651), 체질에 맞는 식품 또는 약품 접촉 시의 손목의 압력(대한민국 등록특허 10-0563127), 또는 수지근력(대한민국 등록실용 2020000032492), 또는 몸의 반응(대한민국 등록실용 20-0365859)을 측정하거나, 음성 신호의 정보를 분석 하여 체형에 관한 정보를 추출하거나(대한민국 공개특허 10-2009-0009430, 대한민국 등록특허 10-0427243), 손목에서의 맥진(대한민국 등록특허 10-0464806, 대한민국 등록특허 10-0672083)을 이용하여 판별을 수행하는 방법들을 개발하여 적용하고자 하는 노력이 있어 왔으나, 적용 원리에 있어서 과학적 근거가 부족하고 측정 정밀도가 낮으며, 체질의 판정 지표 중 극히 일부를 사용하여 판정함으로써 정확도와 재현성 및 신뢰도를 개선하지 못하였다.In order to facilitate the determination of filamentous constitution, conventionally, the physical response of the finger and the contact of gold or silver finger is measured (Korean Patent No. 10-0455996, 20-0325651 for the Republic of Korea Registered Room), or when the food or drug is in contact with the constitution. Information about the body shape by measuring the pressure of the wrist (Korean Patent Registration No. 10-0563127), or resinous muscle strength (Korean Registered Room 2020000032492), or the body's response (Korean Registered Room 20-0365859), or by analyzing information of a voice signal Extracting the method (Korean Patent Application Publication No. 10-2009-0009430, Republic of Korea Patent Registration 10-0427243) or using the pulsation on the wrist (Republic of Korea Patent Registration 10-0464806, Republic of Korea Patent Registration 10-0672083) Although there have been efforts to apply them, there is a lack of scientific basis, low measurement accuracy, and extremely low among the indicators of constitution. Judging from some of them did not improve accuracy, reproducibility, and reliability.
최근에는, 체질문진표(Sasangin diagnosis questionnaire)를 고안하여, 다양한 체질의 판정지표를 체계적으로 종합하여 체질판정을 과학화하고 객관화하고자 하였으며(Jung-Hee Yoo외, J. Alternative and Complementary Medicine, 13(1), 2007), 체질을 유전학적인 면에서 검토하고 조사하여 체질별 상이성 및 상관성을 찾아보고, 체질분류의 객관화를 위한 기초를 마련하려는 연구(조동욱 외, 사상의학회지 8(12), 1996; 이수경 외, 사상체질학회지 14(2), 2002; 한성규 외, 사상체질학회지 15(1), 2003; 김판준 외, 사상체질의학회지 18(3), 2006)가 수행되어 왔다.Recently, Sasangin diagnosis questionnaire was devised to systematically synthesize various constitution indicators to scientificize and objectify the constitution decision (Jung-Hee Yoo et al., J. Alternative and Complementary Medicine, 13 (1)). , 2007), a study to examine and examine constitution in terms of genetics to find differences and correlations between constitutions and to lay the groundwork for objectification of constitution (Cho, Dong-wook et al., Journal of Sasang Medicine 8 (12), 1996; The Journal of Sasang Constitutional Medicine 14 (2), 2002; Han, Sung-Kyu et al., Sasang Constitutional Society Journal 15 (1), 2003; Kim, Pan-Jun et al., Sasang Constitutional Medicine Journal, 18 (3), 2006).
그러나, 이러한 연구들은 사상체질의 유전성을 이용하여 사상체질과 연관된 유전체 부위를 과학적으로 규명하려는 시도로서의 가치가 있으나, 결과적으로는 사상체질과 뚜렷하게 연관된 유전자를 밝히거나 진단에 이용할 수 있는 유전적 지표를 밝혀내지는 못하였다. However, these studies are valuable as an attempt to scientifically identify the genomic region associated with filamentous constitution using the genetics of filamentous constitution, but as a result, genetic markers that can be used to identify or diagnose genes that are clearly associated with filamentous constitution are found. It was not revealed.
이에, 본 발명자들은 상기한 종래의 사상체질 진단 방법의 비과학성,비객관성,낮은 정확도 및 재현성 문제를 개선하기 위해 사상체질의 유전성에 근거하 여 사상체질과 연관된 SNP들을 발굴하기 위한 연구를 진행하던 중, 특정 사상체질의 인구 집단은 특정 SNP들에서 특정 유전형을 가지고 있고, 상기 SNP들의 유전형 정보를 이용하여 개인의 사상체질 확률을 진단할 수 있음을 확인함으로써 본 발명을 완성하였다. Therefore, the present inventors have been researching to discover SNPs related to Sasang Constitution based on heredity of Sasang Constitution to improve the non-scientific, non-objective, low accuracy and reproducibility problems of the conventional Sasang Constitution diagnosis method described above. Among them, the population of a particular filamentous constitution has completed the present invention by confirming that a specific genotype has specific genotypes, and that the genotype information of the SNPs can diagnose the probability of filamentous constitution in the individual.
본 발명의 목적은 사상체질을 진단할 수 있는 다중 SNP(Single Nucleotide Polymorphism) 지표들, 그를 포함하는 탐침을 이용하는 마이크로어레이, 및 그를 이용한 사상체질 진단용 키트를 제공하는 것이다.It is an object of the present invention to provide multiple Nucleotide Polymorphism (SNP) indicators capable of diagnosing filamentous constitution, a microarray using a probe comprising the same, and a kit for filamentous constitution diagnosis using the same.
상기 목적을 달성하기 위하여, 본 발명은 서열번호 1 내지 124로 구성된 폴리뉴클레오티드에 있어서 각 SNP(Single Nucleotide Polymorphism)의 위치(각 서열의 101번째)의 염기를 포함하는 10개 이상의 연속 염기로 구성되는 폴리뉴클레오티드들로부터 선택되는 하나 이상의 폴리뉴클레오티드 또는 그의 상보적 폴리뉴클레오티드를 포함하는, 사상체질 진단용 다중 SNP를 제공한다. In order to achieve the above object, the present invention is composed of 10 or more consecutive bases containing the base of the position (101th of each sequence) of each SNP (Single Nucleotide Polymorphism) in the polynucleotide consisting of SEQ ID NO: 1 to 124 Provided are multiple SNPs for filamentous constitution diagnostics, comprising one or more polynucleotides or complementary polynucleotides thereof selected from polynucleotides.
또한, 본 발명은 상기 SNP의 폴리뉴클레오티드, 그의 상보적 폴리뉴클레오티드, 그들과 혼성화 하는 폴리뉴클레오티드, 또는 그에 의해 코딩되는 폴리펩티드를 포함하는 사상체질 진단용 마이크로어레이를 제공한다.The present invention also provides a microarray for filamentous constitution comprising a polynucleotide of the SNP, a complementary polynucleotide thereof, a polynucleotide hybridizing with them, or a polypeptide encoded by the same.
또한, 본 발명은 상기 마이크로어레이를 포함하는 사상체질 진단용 키트를 제공한다.In addition, the present invention provides a kit for filamentous constitution diagnosis comprising the microarray.
아울러, 본 발명은 1) 피검체로부터 핵산 시료를 분리하는 단계; 2) 상기 핵산 시료를 형광물질로 표지하는 단계; 3) 형광물질로 표지된 핵산시료를 상기 마이크로어레이와 혼성화하는 단계; 3) 반응한 마이크로어레이를 분석하여 서열번호 1 내지 124 중에서 선택되는 하나 이상의 폴리뉴클레오티드의 각 다형성 부위의 유전자형을 결정하는 단계; 및 4) 상기 유전자형을 이용하여 피검체의 사상체질을 결정하는 단계를 포함하는 사상체질 진단 방법을 제공한다.In addition, the present invention 1) separating the nucleic acid sample from the subject; 2) labeling the nucleic acid sample with a fluorescent material; 3) hybridizing a nucleic acid sample labeled with a fluorescent material with the microarray; 3) analyzing the reacted microarrays to determine the genotype of each polymorphic site of at least one polynucleotide selected from SEQ ID NOs: 1 to 124; And 4) provides a filamentous constitution diagnostic method comprising the step of determining the filamentous constitution of the subject using the genotype.
본 발명에 따른 다중 SNP는 사상체질 중 특정한 체질에서만 특이적으로 나타나고 그 외 체질인들에게서는 거의 나타나지 않는 SNP의 특정 조합 및 이들의 유전자형을 가지고 있으므로, 개인의 사상체질을 효과적으로 진단할 수 있다. 특히, 사상체질의 유전성에 근거하여 개인마다 특이적으로 다른 유전적 변이를 정확하게 측정하여 분석한 결과에 근거한 것으로, 본 발명에 따른 다중 SNP, 이를 이용한 마이크로어레이, 및 이를 이용한 사상체질 진단용 키트는 보다 과학적이고, 객관적이며, 정확한 사상체질의 진단을 가능하게 한다.Since multiple SNPs according to the present invention have a specific combination of SNPs and genotypes that are specific only in certain constitutions of filamentous constitution and rarely appear in other constitutions, it is possible to effectively diagnose filamentous constitutions of individuals. In particular, based on the results of accurate measurement and analysis of genetic variation specific to each individual based on the genetic inheritance of filamentous constitution, multiple SNPs according to the present invention, a microarray using the same, and a kit for diagnosing filamentous constitution using the same Scientific, objective and accurate diagnosis of filamentous constitution is possible.
이하, 본 발명을 보다 상세히 설명한다.Hereinafter, the present invention will be described in more detail.
본 발명은 서열번호 1 내지 124로 구성된 폴리뉴클레오티드에 있어서 각 SNP(Single Nucleotide Polymorphism, 단일염기다형성)의 위치(각 서열의 101번째)의 염기를 포함하는 10개 이상의 연속 염기로 구성되는 폴리뉴클레오티드들로부터 선택되는 하나 이상의 폴리뉴클레오티드 또는 그의 상보적 폴리뉴클레오티드를 포 함하는, 사상체질 진단용 다중 SNP를 제공한다.The present invention relates to polynucleotides consisting of 10 or more consecutive bases comprising a base at the position of each SNP (Single Nucleotide Polymorphism) in the polynucleotide consisting of SEQ ID NOs: 1 to 124 (101th of each sequence). Provided are multiple SNPs for filamentous constitution diagnostics, comprising one or more polynucleotides selected from or complementary polynucleotides thereof.
상기 서열번호 1 내지 124로 표시되는 SNP 위치의 염기서열을 포함하는 폴리뉴클레오티드들은 하기 [표 1]에 기재된 바와 같다:Polynucleotides comprising the nucleotide sequence of the SNP position represented by SEQ ID NO: 1 to 124 are as described in Table 1 below:
상기 용어 'SNP'는 개인간의 DNA에 존재하는 한 염기쌍(single base-pair variation)의 차이로 DNA 서열 다형성 중에서 가장 많이 존재하는 형태를 의미한다(약 1개/1kb).The term 'SNP' refers to a form most present among DNA sequence polymorphisms by a single base-pair variation in DNA between individuals (about 1 kb).
상기 용어 'SNP의 dbSNP(The Single Nucleotide Polymorphism Database) 등록번호'는 상기 각 SNP의 서열 및 그 위치를 나타내는 것이다. 당업자라면 상기 등록번호를 이용하여 SNP의 위치 및 서열을 용이하게 확인할 수 있을 것이다. NCBI의 dbSNP에 등록되어 있는 SNP의 rs 번호에 해당하는 구체적인 서열은 시간이 지남에 따라 약간 변경될 수 있다. 본 발명의 범위가 상기 변경된 서열에도 미치는 것은 당업자에게 자명할 것이다.The term dbSNP (Single Nucleotide Polymorphism Database) registration number of the SNP refers to the sequence and location of each of the SNPs. Those skilled in the art will be able to easily identify the position and sequence of the SNP using the registration number. The specific sequence corresponding to the rs number of the SNP registered in the NCBI's dbSNP may change slightly over time. It will be apparent to those skilled in the art that the scope of the present invention also applies to such altered sequences.
상기 '서열번호 1 내지 124'는 다형성 부위를 포함하는 다형성 서열(polymorphic sequence)이다. 다형성 서열이란 폴리뉴클레오티드 서열 중에 SNP를 나타내는 다형성 부위(polymorphic site)를 포함하는 서열을 말한다. 상기 폴리뉴클레오티드 서열은 DNA 또는 RNA가 될 수 있다.'SEQ ID NOS 1 to 124' is a polymorphic sequence including a polymorphic site. A polymorphic sequence refers to a sequence comprising a polymorphic site representing SNP in a polynucleotide sequence. The polynucleotide sequence may be DNA or RNA.
상기 서열번호 1 내지 124로 표시되는 SNP 위치의 염기서열을 포함하는 폴리뉴클레오티드에 존재하는 각 SNP의 특성은 하기 [표 2]에 기재된 바와 같다:The characteristics of each SNP present in the polynucleotide including the nucleotide sequence of the SNP position represented by SEQ ID NOS: 1 to 124 are as described in the following [Table 2]:
dbSNP
등록번호Of SNP
dbSNP
Registration Number
상기 [표 2]에서 용어 '밴드'는 각 단일 SNP가 위치하는 염색체 번호, 각 염색체 상의 동원체를 중심으로 한 단완(short arm; p) 부분 또는 장완(long arm; q) 부분 및 밴드 번호를 의미한다. 예를 들어, 서열번호 1에 포함되어 있는 SNP의 위치는 1p32.3이며, 이는 1번 염색체 상의 단완 부분(p)의 32.3 밴드 상에 존재함을 의미한다.In [Table 2], the term 'band' means a chromosome number where each single SNP is located, a short arm (p) portion or a long arm (q) portion and a band number centered on a chromosome on each chromosome. do. For example, the position of the SNP included in SEQ ID NO: 1 is 1p32.3, which means that it is on the 32.3 band of the forearm portion (p) on chromosome 1.
상기 용어 '유전자'는 각 SNP를 포함하는 유전자를 의미한다.The term 'gene' means a gene comprising each SNP.
상기 용어 'SNP의 역할'은 상기 유전자 내에서 상기 각 단일 SNP가 수행하는 역할을 의미한다.The term 'role of SNP' refers to the role of each single SNP in the gene.
상기 용어 '진단 체질'은 각 SNP를 이용하여 진단에 사용할 수 있는 체질이다. 예를 들어, 서열번호 1에 해당하는 SNP는 소음 체질을 진단하는데 사용될 수 있다. The term 'diagnosis constitution' is a constitution that can be used for diagnosis using each SNP. For example, the SNP corresponding to SEQ ID NO: 1 can be used to diagnose noise constitution.
상기 용어 '유의확률'은 각 SNP가 사상체질 중의 특정 체질에 연관되어 있지 않을 확률을 의미하며, 특정 체질 집단과 나머지 체질 집단 간의 각 SNP의 유전형 분포가 균일하다는 귀무가설 하에서 실제 검사된 유전형 분포가 얻어질 확률을 카이제곱 검정으로 계산한 것이다. 즉, 유의확률의 값이 작을수록 그 SNP가 특정 체질에 깊이 연관되어 있음을 나타내어 준다. 예를 들어, 상기 [표 2]에서 서열번호 1에 해당하는 SNP가 소음 체질에 연관되어 있지 않다는 가정 하에서, 실험적으로 얻어진 유전형 분포가 나타날 확률은 약 0.004에 해당하며, 이것은 서열번호 1에 해당하는 SNP가 소음 체질에 깊이 연관되어 있음을 알 수 있는 것이다. 상기 [표 2]에 나타낸 바와 같이, 서열번호 1 내지 124에 해당하는 SNP들은 유의확률이 0.00008에서 0.005에 이르는 낮은 값으로, 상기의 SNP들이 각 진단체질에 해당하는 사상체질에 깊이 연관되어 있으며, 상기 SNP들의 유전형 정보를 이용하여 사상체질의 진단에 효과적으로 활용할 수 있음을 기대할 수 있다.The term 'significance probability' refers to the probability that each SNP is not related to a specific constitution in filamentous constitution, and the genotype distribution actually tested under the null hypothesis that the genotype distribution of each SNP is uniform between a specific constitution group and the rest of the constitution group The probability to be obtained is calculated by the chi-square test. In other words, the smaller the value of the probability of significance, the more closely the SNP is related to the constitution. For example, under the assumption that the SNP corresponding to SEQ ID NO: 1 in Table 2 is not related to the noise constitution, the probability of the experimentally obtained genotypic distribution is about 0.004, which corresponds to SEQ ID NO: 1 It can be seen that SNP is deeply related to noise constitution. As shown in [Table 2], SNPs corresponding to SEQ ID NOs: 1 to 124 have a low probability ranging from 0.00008 to 0.005, and the SNPs are deeply related to filamentous constitutions corresponding to each diagnosis. It can be expected that the genotype information of the SNPs can be effectively used for the diagnosis of filamentous constitution.
상기 용어 '카이제곱 검정(Chi-square Test)'은 두 변수 사이의 연관성을 평가하기 위하여 교차분석에서 사용하는 통계적 검정으로, 두 변수가 연관성이 없다는 귀무가설 하에서, 표 3에 나타낸 특정 SNP의 집단별 유전형 빈도에 대한 교차 분할표로부터 수학식 1로 계산된 카이제곱 통계량은 자유도가(분할표 컬럼수-1)×(분할표 줄수-1)인 카이제곱 분포를 한다는 것을 이용하여 관측된 데이터가 나올 수 있는 유의 확률을 계산하는 통계적 검정법이다.The term chi-square test is a statistical test used in a crosstab to evaluate the association between two variables. Under the null hypothesis that the two variables are not related, a group of specific SNPs shown in Table 3 The chi-square statistic, calculated from Equation 1 from the cross-partition table for star genotype frequencies, uses the chi-square distribution with degrees of freedom (number of partition columns-1) × (number of partition lines-1). Statistical test to calculate the probability of significance.
본 발명에 따른 사상체질 진단용 다중 SNP에 있어서, 상기 하나 이상의 폴리뉴클레오티드는 서열번호 1 내지 124로 구성된 폴리뉴클레오티드들에 있어서 각 SNP의 위치(각 서열의 101번째) 염기를 포함하는 10개 이상의 연속 염기로 구성되는 폴리뉴클레오티드들로 부터,하기 표 4의 조합으로 선택되는 1 내지 108로 구성된 군에서 선택되는 것이 바람직하다.In the multiple SNP for filamentous constitution diagnosis according to the present invention, the one or more polynucleotides are 10 or more consecutive bases including the position (101st of each sequence) base of each SNP in the polynucleotides consisting of SEQ ID NOs: 1 to 124 From the polynucleotide consisting of, it is preferably selected from the group consisting of 1 to 108 selected from the combination of Table 4 below.
상기 '진단 체질'은 소음, 소양, 태음 중의 한 체질로, '다중 SNP'의 유전형을 이용하여 진단할 수 있는 체질이다. The 'diagnosis constitution' is one of noise, literacy, lume, constitution, which can be diagnosed using the genotype of 'multiple SNP'.
본 발명에 따른 사상체질 진단용 다중 SNP에 있어서, 상기 선택된 폴리뉴클레오티드들의 각 SNP 위치(각 서열의 101번째) 염기의 대립 유전자형은 표 5에 나타낸 대립 유전자형이 바람직하다.In the multiple SNP for filamentous constitution diagnosing according to the present invention, the allele type of each SNP position (101st of each sequence) base of the selected polynucleotides is preferably the allele type shown in Table 5.
상기 용어, '다중 SNP 컬럼'은 선택된 3개의 단일 SNP의 조합을 나타내는 것이고, '대립 유전자형 컬럼'은 동일한 순서의 각 단일 SNP의 SNP 위치에서의 대립 유전자형을 나타낸 것을 의미한다. 예를 들어, 상기 [표 5]의 다중 SNP 1번에 있어서, rs7761051의 유전자형은 AA이고, rs17517219의 유전자형은 AA이며, rs6487998의 유전자형은 AG이다.The term 'multiple SNP column' refers to the combination of three single SNPs selected, and 'allele genotype column' refers to the allele type at the SNP position of each single SNP in the same order. For example, in the multiple SNP No. 1 of Table 5, genotype of rs7761051 is AA, genotype of rs17517219 is AA, and genotype of rs6487998 is AG.
상기 용어, '사상체질'은 소양, 소음, 태양 및 태음을 의미하며, 본 발명이 제공하는 체질의 진단 대상은 소양, 소음 및 태음의 3 체질인 것이 바람직하나 이에 한정되지 않는다. 태양인 체질은 한국인에 있어서 그 빈도가 매우 낮기 때문이다. As used herein, the term "depressive constitution" means literacy, noise, sun and lunation, and the object of diagnosis provided by the present invention is preferably three constitutions of literacy, noise, and lunation, but is not limited thereto. This is because the constitution of the sun is very low in Koreans.
본 발명자들은, 상기 각 단일 SNP들로부터 소양, 소음 및 태음의 각 체질에 연관성이 매우 큰 단일 SNP들의 조합, 즉 다중 SNP를 개발하기 위하여 일련의 선별 과정을 거쳤다. 소양, 소음 및 태음의 각 체질집단에 해당하는 피검자들의 혈액으로부터 DNA를 분리 및 증폭하고, 상기 DNA 중 SNP 위치의 서열을 분석한 다음, 소양, 소음, 태음의 각 체질 집단에서만 특이적으로 나타나고 그 외 집단에서는 거의 나타나지 않는 SNP의 특정 조합 및 그들의 유전자형을 확인하였다. 본 발명의 실시예에서 확인된 각 체질별 SNP 조합 및 그들의 대립 유전자형은 각각 상기 [표 4] 및 [표 5]에 나타내었으며, 각 다중 SNP의 특성에 관하여는 하기 [표 6]에 나타내었다.The present inventors went through a series of screening processes to develop a combination of single SNPs, ie multiple SNPs, from each of the single SNPs, which are highly related to each constitution of literacy, noise, and lupus. DNA is isolated and amplified from the blood of subjects corresponding to each constitutional group of cultivation, noise, and lull, and the sequence of the SNP position in the DNA is analyzed. Specific combinations of SNPs and their genotypes that were seldom seen in the outer population were identified. The SNP combinations and their alleles for each constitution identified in the Examples of the present invention are shown in Tables 4 and 5, respectively, and the characteristics of each of the multiple SNPs are shown in Table 6 below.
상기 [표 6]에 있어서, 용어 '번호'는 다중 SNP의 번호를 나타내는 것으로, 상기 [표 4]에 기재되어 있는 번호와 동일하다.In Table 6, the term 'number' indicates the number of multiple SNPs and is the same as the number described in Table 4 above.
상기 용어 '진단체질'은 사상 체질 중 본 발명에서 다루는 소음, 소양 및 태음 중 하나로서, 상기 '번호'에 해당하는 다중 SNP를 이용하여 체질을 판별하고자 하는 체질을 의미한다.The term 'synagogue' is one of the noise, literacy and lume of the present invention among Sasang constitutions, and means the constitution to determine the constitution using multiple SNPs corresponding to the 'number'.
상기 용어 '출현빈도'는 '관심 체질군'과 '타 체질군' 내에서 해당 다중 SNP를 갖는 것으로 판명된 관심 체질인과 타 체질인 수를 의미한다.The term 'frequency of occurrence' refers to the number of constitutions and other constitutions of interest that have been found to have corresponding multiple SNPs within the 'constitution of interest' and 'other constitutions'.
상기 용어 '오즈비(odds ratio)'는 관심 체질군 중에서 해당 다중 SNP를 가질 확률에 대한 타 체질군 중에서 해당 다중 SNP를 가질 확률의 비율을 의미한다. 즉, 오즈비는 ad/bc로서, 상기 식에서 a는 상기 [표 6]의 1번 다중 SNP의 유전형의 소음인군의 출현 빈도를 나타내고, c는 타 체질군, 즉, 소양, 태음인군의 출현 빈도를 나타낸다. 그리고, b = [(총 소음인 수)-a]이고, d = [(총 타 체질인 수)-c]이다. 시험된 소음인, 소양인, 태음인 군이 각각 91명, 123명 및 173명이므로 결국 b = [91-a]이고, d = [296-c]이다.The term 'odds ratio' refers to the ratio of the probability of having the corresponding multiple SNP among other constitution groups to the probability of having the corresponding multiple SNP in the constitution group of interest. That is, the odds ratio is ad / bc, where a represents the frequency of occurrence of the genotype noise group of the multiplex SNP of Table 6, and c represents the frequency of occurrence of other constitution groups, that is, the Soyang and Taein groups. Indicates. And b = [(number of total noise) -a] and d = [(number of total noise) -c]. The noise tested, Soyangin, and Taeinin groups were 91, 123, and 173, respectively, so b = [91-a] and d = [296-c].
상기 오즈비가 1을 초과하는 경우 해당 다중 SNP가 진단체질과 연관성이 있음을 의미하는 것이다. 오즈비가 클수록 상기 연관성도 증가한다. 상기 [표 6]에 나타난 바와 같이, 본 발명에 따른 다중 SNP 1 내지 108은 39.9 내지 114.8의 오즈비를 갖는다. 이 수치는 1 보다 훨씬 큰 수치이므로, 본 발명에 따른 다중 SNP 1 내지 34는 소음 체질,다중 SNP 35 내지 72은 소양 체질,다중 SNP 73 내지 108은 태음 체질과 큰 연관성이 있음을 알 수 있다.If the odds ratio exceeds 1, it means that the multiple SNPs are associated with the diagnosis. The larger the odds ratio, the higher the association. As shown in Table 6, multiple SNPs 1 to 108 according to the present invention have an odds ratio of 39.9 to 114.8. Since this value is much larger than 1, it can be seen that the multi-SNP 1 to 34 according to the present invention is a noise constitution, the multiple SNP 35 to 72 is a small body constitution, the multiple SNP 73 to 108 is significantly associated with the Taeum constitution.
상기 용어 '95% 신뢰구간'은 해당 오즈비가 존재할 확률이 95%인 구간을 의미하는 것으로서, 하기 [수학식 2]와 같이 계산된다. 신뢰구간이 1을 포함하는 경우, 즉 신뢰구간의 하계가 1 이하이고 상계가 1 이상인 경우에는 각 진단체질과의 연관성이 유의하다고 판단할 수 없다.The term '95% confidence interval 'means a section having a 95% probability that the odds ratio exists, and is calculated as shown in Equation 2 below. If the confidence interval contains 1, that is, if the lower bound of the confidence interval is less than 1 and the upper bound is greater than or equal to 1, the association with each group cannot be considered significant.
(여기서, V = 1/a + 1/b + 1/c + 1/d )Where V = 1 / a + 1 / b + 1 / c + 1 / d
상기 용어 '유의확률'은 각 다중 SNP의 유전형 분포가 관심 체질군과 타 체질군 사이에서 차이가 없다는 귀무가설 하에서 계산한, 각 다중 SNP의 유전형 빈도가 측정결과와 같이 얻어질 확률을 의미한다.The term 'significance probability' refers to the probability that the genotype frequency of each multiple SNP is obtained as the measurement result, calculated under the null hypothesis that the genotype distribution of each multiple SNP does not differ between the group of constitution and other groups of interest.
상기 용어 '자유도'는 상기 '유의확률'을 계산하기 위하여 사용된 카이제곱 분포의 자유도를 의미한다. 즉, 유의확률이 낮을수록 측정에서 얻어진 다중 SNP의 유전형 빈도가 관심 체질군과 타 체질군에서 다르게 나타남을 의미한다.The term 'freedom' refers to the degree of freedom of the chi-square distribution used to calculate the 'significance probability'. In other words, the lower the probability of significance, the more likely the genotype frequency of the multiple SNPs obtained from the measurements is shown in the constitution group of interest and other constitution groups.
본 발명의 사상체질 진단용 다중 SNP는 상기 다중 SNP 각각으로 구성될 수 있고, 더욱 바람직하게는 2개 이상의 다중 SNP로 구성될 수 있으며, 가장 바람직하 게는 상기 다중 SNP 1 내지 108개 전부로 구성될 수 있으나 이에 한정되는 것은 아니다.The multiple SNP for filamentous constitution diagnosis of the present invention may be composed of each of the multiple SNPs, more preferably, two or more multiple SNPs, and most preferably, all of the multiple SNPs 1 to 108 But it is not limited thereto.
본 발명의 사상체질 진단용 다중 SNP를 구성하는 각 단일 SNP의 폴리뉴클레오티드는 10개 이상의 연속 염기인 것이 바람직하고, 10 내지 100개의 연속 염기인 것이 더욱 바람직하나 이에 한정되지 않는다.The polynucleotide of each single SNP constituting the multiple SNP for filamentous constitution diagnostic diagnosis of the present invention is preferably 10 or more consecutive bases, more preferably 10 to 100 consecutive bases, but is not limited thereto.
또한, 본 발명은 상기 SNP의 폴리뉴클레오티드, 그의 상보적 폴리뉴클레오티드, 그들과 혼성화하는 폴리뉴클레오티드, 또는 그에 의해 코딩되는 폴리펩티드를 포함하는 사상체질 진단용 마이크로어레이를 제공한다.The present invention also provides a microarray for filamentous constitution comprising a polynucleotide of the SNP, a complementary polynucleotide thereof, a polynucleotide hybridizing thereto, or a polypeptide encoded by the SNP.
상기 SNP의 폴리뉴클레오티드, 그의 상보적 폴리뉴클레오티드, 그들과 혼성화하는 폴리뉴클레오티드는 10개 이상의 연속 염기인 것이 바람직하고, 10 내지 100개의 연속 염기인 것이 더욱 바람직하나 이에 한정되지 않는다.The polynucleotide of the SNP, its complementary polynucleotide, and the polynucleotide hybridizing thereto are preferably 10 or more consecutive bases, more preferably 10 to 100 consecutive bases, but are not limited thereto.
상기 사상체질 진단용 마이크로어레이는 서열번호 1 내지 124의 각 다형성 서열 중의 다형성 부위의 염기를 특이적으로 구별할 수 있도록 혼성화할 수 있는 폴리뉴클레오티드, 그의 상보적 폴리뉴클레오티드, 또는 그들과 혼성화하는 폴리뉴클레오티드, 그에 의해 코딩되는 폴리펩티드 또는 그의 cDNA를 이용하여 프로브로 사용함으로써, 당업자에게 알려져 있는 통상적인 방법에 의해 제조될 수 있다. The filamentous constitution diagnostic microarray is a polynucleotide capable of hybridizing to specifically distinguish a base of a polymorphic site in each polymorphic sequence of SEQ ID NOs: 1 to 124, a complementary polynucleotide thereof, or a polynucleotide hybridizing with them, By using the polypeptide encoded therein or the cDNA thereof as a probe, it can be prepared by conventional methods known to those skilled in the art.
상기 폴리뉴클레오티드는 아미노-실란(amino-silane), 폴리-L-라이신(poly-L-lysine) 및 알데히드(aldehyde)로 이루어진 군에서 선택되는 하나의 활성기가 코팅된 기판 상에 고정되는 것이 바람직하나 이에 한정되는 것은 아니다. Preferably, the polynucleotide is immobilized on a substrate coated with one active group selected from the group consisting of amino-silane, poly-L-lysine, and aldehyde. It is not limited to this.
상기 기판은 실리콘 웨이퍼, 유리, 석영, 금속 및 플라스틱으로 이루어진 군으로부터 선택되는 어느 하나를 사용하는 것이 바람직하나 이에 한정되지 않는다. The substrate is preferably, but not limited to, any one selected from the group consisting of silicon wafers, glass, quartz, metals and plastics.
상기 폴리뉴클레오티드를 기판에 고정화시키는 방법으로는 피에조일렉트릭(piezoelectric) 방식을 이용한 마이크로피펫팅(micropipetting)법, 핀(pin) 형태의 스팟터(spotter)를 이용한 방법 등을 사용하는 것이 바람직하나 이에 한정되지 않는다.As a method of immobilizing the polynucleotide on a substrate, it is preferable to use a micropipetting method using a piezoelectric method, a method using a pin type spotter, etc., but not limited thereto. It doesn't work.
상기 마이크로어레이의 이용과 제작은 당업계에서는 보편화되어 제공되고 있으며, 본 발명의 서열과 같이 프로브 제작을 위한 용도가 밝혀진 변이 부위의 정보를 가진 당업자들은 용이하게 마이크로어레이의 제작과 연구적 사용이 가능할 것이다.The use and fabrication of the microarray has been widely provided in the art, and those skilled in the art having the information of the mutant sites that have been found to be used for the fabrication of probes, such as the sequences of the present invention, may readily manufacture and research microarrays. will be.
또한, 본 발명은 본 발명의 마이크로어레이를 포함하는 사상체질 진단용 키트를 제공한다.The present invention also provides a kit for filamentous constitution diagnosis comprising the microarray of the present invention.
상기 사상체질 진단용 키트는 당업자에게 알려져 있는 통상적인 방법으로 제조될 수 있으며, 상기 마이크로어레이 이외에 피검체로부터 해당 SNP를 포함하는 DNA를 분리 및 증폭하는데 사용되는 프라이머 세트를 추가로 포함할 수 있다. The filamentous constitution diagnostic kit may be prepared by a conventional method known to those skilled in the art, and may further include a primer set used to separate and amplify DNA containing a corresponding SNP from a subject in addition to the microarray.
상기 적절한 프라이머 세트는 본 발명의 서열을 참조하여 당업자가 용이하게 설계할 수 있다.Such suitable primer sets can be readily designed by those skilled in the art with reference to the sequences of the present invention.
본 발명의 다중 SNP를 이용하면 개인의 사상체질을 효과적으로 진단할 수 있다. 구체적으로, 피검체로부터 핵산 시료를 분리하고 서열번호 1 내지 124 중에서 선택되는 하나 이상의 폴리뉴클레오티드의 각 SNP 위치(각 서열의 101번째) 염기인 다형성 부위의 유전자형을 결정하여 사상체질을 진단할 수 있다.By using the multiple SNP of the present invention, it is possible to effectively diagnose an individual's filamentous constitution. Specifically, filamentous constitution can be diagnosed by separating the nucleic acid sample from the subject and determining the genotype of the polymorphic site, which is the base of each SNP position (101st of each sequence) of one or more polynucleotides selected from SEQ ID NOs: 1 to 124. .
상기 키트에 추가적으로 형광물질을 포함할 수 있으며, 상기 형광물질은 스트렙아비딘-알칼리 탈인화효소 접합물질(strepavidin-like phosphatease conjugate), 화학형광물질(chemiflurorensce) 및 화학발광물질(chemiluminescent)로 이루어진 군으로부터 선택되는 것이 바람직하나 이에 한정되는 것은 아니며, 본 발명의 바람직한 실시예에서는 Cy3을 사용하였다. The kit may further include a fluorescent material, wherein the fluorescent material is selected from the group consisting of a strepavidin-like phosphatease conjugate, a chemiflurorensce and a chemiluminescent material. Preferably, but not limited thereto, Cy3 was used in the preferred embodiment of the present invention.
상기 키트에 추가적으로 반응 시약을 포함시킬 수 있으며, 상기 반응 시약은 혼성화에 사용되는 완충용액, RNA로부터 cDNA를 합성하기 위한 역전사효소, cNTPs 및 rNTP(사전 혼합형 또는 분리 공급형), 형광 염색제의 화학적 유도제와 같은 표식시약, 세척 완충용액 등으로 구성될 수 있으나 이에 한정된 것은 아니며, 당업자에게 알려진 DNA 마이크로어레이 칩의 혼성화 반응에 필요한 반응 시약은 모두 포함시킬 수 있다.The kit may additionally include a reaction reagent, which is a buffer used for hybridization, reverse transcriptase for synthesizing cDNA from RNA, cNTPs and rNTP (premixed or separated feed), chemical inducer of fluorescent dyes It may be composed of a labeling reagent, such as a washing buffer, but is not limited thereto, and may include all reaction reagents required for hybridization of DNA microarray chips known to those skilled in the art.
아울러, 본 발명은 본 발명의 다중 SNP를 이용하여 사상체질을 진단하는 방법을 제공한다.In addition, the present invention provides a method for diagnosing filamentous constitution using multiple SNPs of the present invention.
구체적으로, Specifically,
1) 피검체로부터 핵산 시료를 분리하는 단계; 1) separating the nucleic acid sample from the subject;
2) 상기 핵산 시료를 형광물질로 표지하는 단계; 2) labeling the nucleic acid sample with a fluorescent material;
3) 형광물질로 표지된 핵산시료를 본 발명의 마이크로어레이와 혼성화하는 단계; 3) hybridizing a nucleic acid sample labeled with a fluorescent material with the microarray of the present invention;
3) 반응한 마이크로어레이를 분석하여 서열번호 1 내지 124 중에서 선택되는 하나 이상의 폴리뉴클레오티드의 각 다형성 부위의 유전자형을 결정하는 단계; 및3) analyzing the reacted microarrays to determine the genotype of each polymorphic site of at least one polynucleotide selected from SEQ ID NOs: 1 to 124; And
4) 상기 유전자형을 이용하여 피검체의 사상체질을 결정하는 단계를 포함하는 사상체질 진단하기 위해, 본 발명의 다중 SNP를 검출하는 방법을 제공한다.4) provides a method for detecting multiple SNPs of the present invention for diagnosing filamentous constitution including the step of determining filamentous constitution using the genotype.
상기 방법에 있어서, 피검체로부터 DNA를 분리하는 방법은 당업계에 알려진 통상적인 방법으로 행할 수 있다. 예를 들어, 조직 또는 세포로부터 DNA를 직접적으로 정제하거나 PCR과 같은 증폭 방법을 사용하여 특정한 영역을 특이적으로 증폭하고 이를 분리함으로써 이루어질 수 있다. In the above method, the method of separating DNA from the subject can be carried out by conventional methods known in the art. For example, it can be done by directly purifying DNA from tissue or cells or by specifically amplifying and isolating specific regions using amplification methods such as PCR.
상기 방법에 있어서, DNA는 DNA 뿐만 아니라 mRNA로부터 합성되는 cDNA도 포함하는 것이다. 피검체로부터 핵산을 얻는 방법은 PCR 증폭법, 리가제 연쇄 반응(LCR)(Wu 및 Wallace, Genomics 4, 560(1989), Landegren 등, Science 241, 1077(1988)), 전사증폭(transcription amplification)(Kwoh 등, Proc. Natl. Acad. Sci. USA 86, 1173(1989)) 및 자가유지 서열 복제(Guatelli 등, Proc. Natl. Acad. Sci. USA 87, 1874(1990)) 및 핵산에 근거한 서열 증폭(NASBA)이 사용될 수 있다. In this method, DNA includes not only DNA but also cDNA synthesized from mRNA. Methods for obtaining nucleic acids from a subject include PCR amplification, 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)) and self-sustaining sequence replication (Guatelli et al., Proc. Natl. Acad. Sci. USA 87, 1874 (1990)) and sequences based on nucleic acids Amplification (NASBA) can be used.
상기 방법에 있어서, 형광물질은 Cy3, Cy5, FITC(poly L-lysine-fluorescein isothiocyanate), RITC(rhodamine-B-isothiocyanate) 및 로다민(rhodamine)으로 이루어진 군으로부터 선택되어지는 것이 바람직하나 이에 한정되는 것은 아니며, 당업자에게 알려진 형광물질은 모두 사용 가능하다.In the above method, the fluorescent material is preferably selected from the group consisting of Cy3, Cy5, poly L-lysine-fluorescein isothiocyanate (FITC), rhodamine-B-isothiocyanate (RITC), and rhodamine (rhodamine). Not all phosphors known to those skilled in the art can be used.
상기 방법에 있어서, 분리된 DNA의 염기서열의 결정은 당업계에 알려진 다 양한 방법에 의하여 이루어질 수 있다. 예를 들면, 디데옥시 법에 의하여 직접적인 핵산의 뉴클레오티드 서열의 결정을 통하여 이루어지거나 SNP 위치의 서열을 포함하는 프로브 또는 이에 상보적인 프로브를 상기 DNA와 혼성화시키고 이로부터 얻어지는 혼성화 정도를 측정함으로써 다형성 부위의 뉴클레오티드 서열을 결정하는 방법 등이 이용될 수 있다. In this method, the determination of the base sequence of the isolated DNA can be made by a variety of methods known in the art. For example, by using the dideoxy method to determine the nucleotide sequence of a nucleic acid or a probe comprising a sequence of the SNP position or a complementary probe to the DNA and by measuring the degree of hybridization resulting from the hybridization of the polymorphic site Methods for determining the nucleotide sequence may be used.
상기 방법에 있어서, 혼성화의 정도는 검출가능한 표지를 표적 DNA에 표지하여, 혼성화된 표적 DNA 만을 특이적으로 검출함으로써 이루어질 수 있으나, 그외 전기적 신호 검출방법 등이 사용될 수 있다. 보다 바람직하게, 상기 피검체로부터 분리한 핵산 시료를 본 발명에 따른 SNP를 포함하는 폴리뉴클레오티드 또는 이의 상보적 폴리뉴클레오티드, 또는 이와 혼성화하는 폴리뉴클레오티드와 혼성화시킨 후 혼성화 결과를 검출하는 단계를 포함할 수 있다.In the above method, the degree of hybridization may be achieved by labeling a target DNA with a detectable label to specifically detect only the hybridized target DNA, but other electric signal detection methods may be used. More preferably, the method may comprise hybridizing a nucleic acid sample isolated from the subject to a polynucleotide comprising a SNP according to the present invention or a complementary polynucleotide thereof, or a polynucleotide hybridizing thereto, and then detecting a hybridization result. have.
상기 방법에 있어서, 사상체질의 진단은 상기 서열번호 1 내지 124 중에서 선택되는 하나 이상의 폴리뉴클레오티드의 다형성 부위의 유전자형이 상기 [표 5]의 1 내지 108 중 하나 이상인 경우 상기 피검체를 해당 진단체질 군에 속하는 것으로 판정할 수 있다. In the above method, the diagnosis of filamentous constitution is performed when the genotype of the polymorphic site of one or more polynucleotides selected from SEQ ID NOs: 1 to 124 is one or more of 1 to 108 in Table 5, and the subject is included in the diagnostic constitution group. Can be determined to belong to.
이하, 본 발명을 실시예에 의해 상세히 설명한다. Hereinafter, the present invention will be described in detail by way of examples.
단, 하기 실시예는 본 발명을 예시하는 것일 뿐 본 발명을 한정하는 것은 아니다.However, the following Examples are only for illustrating the present invention and do not limit the present invention.
<실시예 1> 본 발명의 다중 SNP의 선별Example 1 Screening of Multiple SNPs of the Present Invention
본 발명자들은 한국인 중 3인의 사상체질 전문가들에 의하여 공통적으로 소음인, 소양인, 태음인 또는 태양인으로 판정된 사상 체질 분류자들의 혈액으로부터 DNA를 분리하고, SNP 마이크로어레이를 이용하여 유전형 검사를 수행하였으며, 검사가 수행된 SNP들의 유전형 데이터로부터 3개의 SNP의 조합으로 이루어지는 조합 중에서 환자군에서 특이적으로 나타나는 조합을 통계적으로 분석하여 사상체질 중 태양인을 제외한, 소음인, 소양인 또는 태음인 체질을 진단할 수 있는 다중 SNP를 선별하였다.We isolated DNA from the blood of Sasang Constitution Classifiers that were commonly determined to be noise, Soyang, Taein or Sun by three Sasang constitution experts among Koreans, and performed genotyping using SNP microarrays. In the combination consisting of three SNPs from the genotype data of the SNPs performed, statistically analyzing the combinations appearing specifically in the patient group, the multiple SNPs capable of diagnosing noise, soyangin, or lunium constitution except for Sunin among Sasang constitutions. Screened.
<1-1> DNA 시료의 준비<1-1> DNA Sample Preparation
한국한의학연구원내의 체질유전자은행으로부터 사상체질이 분류된 소음인 91명, 소양인 123명, 태음인 173명, 태양인 3명의 혈액으로부터 추출한 genomic DNA를 분양받아 사용하였다. 염색체 DNA 추출은 공지의 추출 방법(Molecular cloning: A Laboratory Manual, p392, Sambrook, Fritsch and Maniatis, 2nd edition, Cold Sping Harbor Press, 1989)과 상업용 키트(Gentra system, D-50K)(Gentra Inc., USA)의 설명서에 따라 이루어졌다. 추출된 DNA 중 순도 기준이 UV 측정비율(260/280 nm)로 최소 1.7 이상 되는 것만을 선별하여 사용하였다.Genomic DNA extracted from the blood of 91 people, Saeyang 123, Taeeum 173, and Sun 3 were classified and classified by Sasang Constitution from the Constitutional Gene Bank of Korea Institute of Oriental Medicine. Chromosome DNA extraction was performed using known extraction methods (Molecular cloning: A Laboratory Manual, p392, Sambrook, Fritsch and Maniatis, 2nd edition, Cold Sping Harbor Press, 1989) and commercial kits (Gentra system, D-50K) (Gentra Inc., USA). Among the extracted DNA, the purity standard was selected and used only at least 1.7 in the UV measurement ratio (260/280 nm).
<1-2> SNP의 유전형(genotype) 분석<1-2> Genotype Analysis of SNPs
SNP의 유전자형 검사는 약 50만개의 프로브가 고정된 마이크로어레이 (GeneChip Human Mapping 500K Array Set 및 5.0 Set, 및 GeneChip Fluidics Station 450 시스템)(Affymetrix, USA)를 이용하여 수행하였다.Genotyping of SNPs was performed using a microarray (GeneChip Human Mapping 500K Array Set and 5.0 Set, and GeneChip Fluidics Station 450 system) (Affymetrix, USA) to which about 500,000 probes were immobilized.
<1-3> 다중 SNP의 선별<1-3> Screening of Multiple SNPs
상기 실시예 <1-2>에서 분석한 91명의 소음인, 123명의 소양인, 및 173명의 태음인에 대하여 수행한 마이크로어레이를 이용한 유전형 검사결과를 기초로 하여, 각 체질 별로 자주 발견되는 SNP의 조합, 즉 다중 SNP를 선별하였다.On the basis of genotyping results using microarrays performed on 91 noise persons, 123 yangyang, and 173 taeumin analyzed in Example <1-2>, that is, a combination of SNPs frequently found in each constitution, ie Multiple SNPs were selected.
먼저, 상기 마이크로어레이를 이용한 유전형 검사로부터 387명에 대한 440,974개의 SNP에 대한 유전형 데이터를 얻었다. 단일 SNP 마커를 사용하는 것보다 다중 SNP 마커를 사용하는 것이 표현형에 대한 판별력이 증가하므로 본 발명에서는 3개의 SNP가 조합된 다중 SNP 마커를 사용하고자 하였으며, 이 경우 440,974개의 SNP의 조합으로부터 얻어지는 3중 SNP 마커의 가짓수는 8.6 × 1016 가지에 해당하므로 주어진 전산자원과 기간으로는 분석이 용이하지 않았다. 따라서, 일차적으로 단일 SNP에 대한 연관분석(association study)을 통하여 사상체질과 통계적으로 유의하게 연관된 SNP들을 선별하여 SNP의 개수를 줄이고, 축소된 SNP 집단 내에서의 다중 SNP 마커 조합에 대하여 사상체질과의 연관성을 심도있게 분석하는 2단계의 과정을 수행하였다. 일차로, 연관분석 프로그램인 plink(Shaun Purcell외, http://pngu.mgh.harvard.edu/~purcell/plink/)를 이용하여 사상체질에 연관된 SNP 들을 분석하였다. 전처리 단계에서 하디-와인버그 평형 검사(Hardy-Weinberg equilibrium test)에서 26,133개의 SNP가 제외되었고(유의확률 ≤ 0.0001), 결측치를 10% 이상 포함하고 있는 8,202개의 SNP가 제외되었으며, maf(minor allele frequency)가 5% 미만인 125,743개의 SNP를 제외하여 총 305,803개의 SNP를 대상으로 연관분석을 수행하였다. 그 결과로부터 일차적으로 소음, 소양 또는 태음인을 각각 진단 체질로하는 유의확률이 0.005 보다 작은 사상체질 연관 SNP를 소음인 873개, 소양인 796개, 및 태음인 805개를 각각 선별하였다. 선별된 사상체질 연관 SNP들로부터 3개의 SNP 조합으로 얻어지는 다중 마커의 수는 연관 SNP수가 가장 많은 소음인의 경우 약 1.1×108 가지이며, 이는 일반적인 전산자원과 처리기간을 이용하여 처리할 수 있는 양으로 판단되었다. 각 진단 체질별로 선정한 사상체질 연관 SNP들로부터 3개씩의 SNP 조합으로 얻어지는 다중 SNP 마커에 대하여, 소음, 소양 또는 태음인군을 각각 진단체질군으로 하고, 그 외 체질을 타체질군으로 하여 진단체질군과 타체질군 사이의 유전형 데이터 빈도에 대한 오즈비(odds ratio)와 그에 대한 95% 신뢰구간을 분석하여 다중 마커의 위험요인 정도를 평가하였으며, 카이제곱 검정(chi-square test)을 통하여 그에 대한 통계적 유의성을 평가하였다.First, genotyping data for 440,974 SNPs for 387 were obtained from the genotyping using the microarray. In the present invention, the use of multiple SNP markers increases the discrimination ability of phenotypes rather than the use of a single SNP marker. In the present invention, it is intended to use multiple SNP markers in which three SNPs are combined. Since the number of SNP markers corresponds to 8.6 × 10 16 , it was not easy to analyze the given computational resources and duration. Therefore, SNPs were selected by selecting SNPs that are statistically significantly associated with filamentous constitution through an association study of a single SNP, and the filamentous constitution with respect to the combination of multiple SNP markers in a reduced SNP population. A two-step process of in-depth analysis was performed. First, SNPs related to filamentous constitution were analyzed using plink (Shaun Purcell et al., Http://pngu.mgh.harvard.edu/~purcell/plink/ ). In the pretreatment step, the Hardy-Weinberg equilibrium test excluded 26,133 SNPs (significance ≤ 0.0001), excluded 8,202 SNPs containing more than 10% missing values, and the minor allele frequency (maf). Association analysis was performed on a total of 305,803 SNPs, excluding 125,743 SNPs with less than 5%. From the results, 873 noises, 796 cattles, and 805 lumens were selected for Sasang Constitution-related SNPs with a significance probability of less than 0.005, respectively. The number of multiple markers obtained from a combination of three SNPs from selected filamentous constitutional SNPs is about 1.1 × 10 8 for the noise group with the highest number of associated SNPs, which can be processed using general computational resources and processing periods. Judging by For multi-SNP markers obtained by combining three SNPs from Sasang Constitution-related SNPs selected by each constitution, each group of noise, small, or Taeumin group is used as the diagnosis group, and the other group is the other group. The odds ratio for the frequency of genotyping data and the 95% confidence intervals for the frequency of genotyping data were analyzed to evaluate the risk factors of the multiple markers and the chi-square test. Statistical significance was evaluated.
이때, 오즈비는 어느 한 유전자형을 갖거나 갖지 않는 관심 체질인 및 타 체질인의 수가 각각 하기 [표 7]과 같은 경우에 오즈비 = ad/bc로 나타낸다(오즈비가 1을 초과하는 경우 상기 유전자형은 진단체질과 깊이 연관 되어 있음을 의미한다).In this case, the odds ratio is represented by oz ratio = ad / bc when the number of constitutions and other constitutions of interest having or not having any genotype is as shown in [Table 7], respectively. Means deeply related to the diagnosis.
각 진단 체질별로 선별된 사상체질 연관 SNP들의 조합으로 얻어진 소음인 약 1.1× 108 개, 소양인 약 8.4× 107 개, 태음인 약 8.7× 107 개의의 다중 SNP에 대해 오즈비와 그에 대한 95% 신뢰구간을 계산하여 하계가 2.0 이상인 것을 선별하고, 카이제곱검정에 의한 유의확률이 10-5보다 작은 다중 SNP 마커 108개를 최종 선별하였다. 상기 108개의 다중 SNP는 [표 4] 내지 [표 5]에 나타내었다.Ozbi and its 95% confidence in multiple SNPs of approximately 1.1 × 10 8 noise, approximately 8.4 × 10 7 , and approximately 8.7 × 10 7 noises obtained from a combination of filamentous constitution-related SNPs selected for each diagnostic constitution Sections were calculated to select summers of 2.0 or more, and 108 multiple SNP markers with a significant probability less than 10 −5 by chi-square test were finally selected. The 108 multiple SNPs are shown in [Table 4] to [Table 5].
<실시예 2> 본 발명의 다중 SNP가 고정된 마이크로어레이의 제작Example 2 Fabrication of Multiple SNPs Fixed Microarray of the Present Invention
본 발명자들은 상기 <실시예 1>에서 선별된 다중 SNP를 기판 상에 고정하여 마이크로어레이를 제작하였다. 즉, 상기 [표 1]에 나타낸 각 서열번호로 구성된 폴리뉴클레오티드에서 각 SNP 위치(각 서열의 101번째) 염기를 포함하는 20개의 연속 염기로 구성되는 폴리뉴클레오티드들(각 SNP는 상기 20개 중 11번째에 위치 함)을 기판상에 고정하였다. 각 SNP 위치에 두 개의 대립형질이 존재하므로 각 서열마다 2개씩의 폴리뉴클레오티드를 기판상에 고정화하였다.The present inventors prepared a microarray by fixing the multiple SNPs selected in Example 1 on a substrate. That is, polynucleotides composed of 20 consecutive bases including each SNP position (101st of each sequence) base in the polynucleotide consisting of each SEQ ID NO shown in Table 1 above (each SNP is 11 out of 20). In the second) was fixed on the substrate. Since two alleles exist at each SNP position, two polynucleotides for each sequence were immobilized on the substrate.
구체적으로, 상기 20개의 연속 염기로 구성되는 각 폴리뉴클레오티드의 N-말단을 아민기로 치환한 다음, 실릴화 슬라이드(Telechem사)에 스팟팅하였으며, 이때 상기 스팟팅 버퍼는 2×SSC(saline-sodium citrate, pH 7.0)를 사용하였다. 스팟팅 후 건조기에 두어 결합을 유도한 다음, 0.2% SDS(sodium dodecyl sulfate) 용액으로 2분간, 3차 증류수로 2분간 각각 세척하여 결합되지 않는 올리고를 제거하였다. 상기 슬라이드를 95℃에서 2분간 처리하여 변성을 유도한 후, 블로킹 용액[1.0g NaBH4, PBS(pH 7.4) 300 mL, EtOH 100 mL]으로 15분간, 0.2% SDS 용액으로 1분간, 3차 증류수로 2분간 각각 세척하고 상온에서 건조시켜 마이크로어레이를 제작하였다.Specifically, the N-terminus of each polynucleotide consisting of 20 consecutive bases was substituted with an amine group, and then spotted on a silylated slide (Telechem), wherein the spotting buffer was 2 × SSC (saline-sodium). citrate, pH 7.0). After spotting, the mixture was placed in a dryer to induce binding, followed by washing with 0.2% SDS (sodium dodecyl sulfate) solution for 2 minutes and tertiary distilled water for 2 minutes to remove unbound oligos. The slides were treated at 95 ° C. for 2 minutes to induce denaturation, followed by 15 minutes with blocking solution [1.0 g NaBH 4 , PBS (pH 7.4) 300 mL, EtOH 100 mL], 1 minute with 0.2% SDS solution, 3rd Each was washed with distilled water for 2 minutes and dried at room temperature to prepare a microarray.
<실시예 3> 다중 SNP가 고정된 마이크로어레이를 이용한 사상체질 진단Example 3 Sasang Constitution Diagnosis Using Microarrays with Multiple SNPs
본 발명자들은 사상체질을 진단하고자 하는 대상의 혈액으로부터 표적 DNA를 분리하고, Cy3-dUTP(Metabion 사)로 형광 표지시켰다. UniHyb 혼성화 용액(TeleChem 사) 하에서 상기 <실시예 2>에서 제조된 마이크로어레이와 형광 표지된 표적 DNA의 혼성화를 42℃에서 4시간 동안 수행하였다. 2×SSC로 실온에서 5분간 두 번 세척한 후 공기 중에서 건조시켰다. 건조 후 슬라이드를 스캔어레이 5000(ScanArray 5000; GSI Lumonics 사)으로 스캔하고 스캔 결과를 퀀트어레이(QuantArray)(GSI Lumonics 사)와 ImaGene 소프트웨어(BioDiscover사)로 분석하였다. 그 결과, 상기 대상이 본 발명에 따른 다중 SNP 전부 또는 일부를 갖고 있는지 확인하였으며, 그 대상을 소음인, 소양인 또는 태음인 중 하나의 체질로 판정할 수 있었다.We isolated the target DNA from the blood of the subject to diagnose filamentous constitution and fluorescently labeled it with Cy3-dUTP (Metabion). Under the UniHyb hybridization solution (TeleChem), hybridization of the microarray prepared in <Example 2> with the fluorescently labeled target DNA was performed at 42 ° C. for 4 hours. It was washed twice with 2 x SSC for 5 minutes at room temperature and then dried in air. After drying, the slides were scanned with ScanArray 5000 (GSI Lumonics) and the scan results were analyzed with QuantArray (GSI Lumonics) and ImaGene software (BioDiscover). As a result, it was confirmed whether the subject had all or part of the multiple SNPs according to the present invention, and the subject could be determined as one of noise, yangyang, and Taeinin.
본 발명에 따른 다중 SNP, 이를 이용한 마이크로어레이, 및 이를 이용한 사상체질 진단용 키트는 유전체 변이를 이용하여 신속하고, 객관적이며, 정확한 사상체질의 진단을 가능하게 함으로써 사상체질 진단 확률 및 유전적 감수성을 보다 정확하게 예측하게 하여 대체의학 관련 산업 개발에 기여할 수 있다.Multiple SNPs, a microarray using the same, and a kit for diagnosing filamentous constitution using the same according to the present invention enable the rapid, objective, and accurate diagnosis of filamentous constitution using genome mutations, thereby increasing the probability of filamentous constitution diagnosis and genetic susceptibility. Accurate predictions can contribute to the development of alternative medicine-related industries.
<110> Korea Research Institute of Bioscience and Biotechnology <120> Multiple SNP markers, microarray and diagnosis method for Sasang constitution <130> 9p-05-06 <160> 124 <170> KopatentIn 1.71 <210> 1 <211> 201 <212> DNA <213> Homo sapiens <400> 1 tggggatcct tacaggccac tcacaatggt aatgagagtc cacatttact gagcactcac 60 tacacaccag ccactcttct caagggcttt ccatgtggaa ytgcaccaaa tccttacaac 120 aaccctctga ggctggggct ggtgctgtat ccattctaca gaggaggaac ctgagacaag 180 gaagggtgag ggcttgccaa g 201 <210> 2 <211> 201 <212> DNA <213> Homo sapiens <400> 2 tggagccaac aaaccttccc tttagcatgg gcctagcgct cccttgccca ctgccagctt 60 tgttactctt agatccttaa tctctgttaa tctgatgact rtaaagcaaa aggttacttt 120 aatttgcatt ttcctggcaa ctggggagag gctgcatctt ttcaggtcat tgtgtgtctt 180 gtttcctctt ctgataattg c 201 <210> 3 <211> 201 <212> DNA <213> Homo sapiens <400> 3 ccaacttcaa attttgaacc tgtttaggga tctgttaatt aaagcagccc ctgcctccca 60 cacatccttc tcctctctgt ttttgttatc tactttcttc ratatggatt agccacttac 120 ttgaattaat ctgtttttca actttcaaaa gttagttaaa tttcccagta ttttggtgtg 180 cctactttgt tttttgacat t 201 <210> 4 <211> 201 <212> DNA <213> Homo sapiens <400> 4 ctggtctacg gtatttttgt tatagcagtc tgaactaacg aagacatatg gtactccata 60 ctggtgagaa aggttcttct cagcaagcct cattcttttt ygctttttga aaacctattt 120 ttttcttttt aaaaaaatcc catggcagca tattaatttt tttttctacc tggcagcaga 180 tcagattctt ttgccatggc t 201 <210> 5 <211> 201 <212> DNA <213> Homo sapiens <400> 5 ctttgcttgc aggaagcagt gcaaactgta ttttggaaca caggttcttt ctgacctggg 60 tccttatctt ctgccattta cctcttggaa gacttacgtt stactgacgc tggactactt 120 gacatttcct atccaagttg tgtctccagg cccttatcta tgctgctccc actgcctgga 180 ataccctttc cctctgccat g 201 <210> 6 <211> 201 <212> DNA <213> Homo sapiens <400> 6 actattgtcc cttcctgaag aaggaagtct agtcttcagg taagaggaag gtatattctt 60 aggcagctgc tgggttggaa ggaaggaaca gtgaagtctg ygttttggaa gggaggaggg 120 agtgacattt ttaagttaca agcctcttct gggagagctg gggacagatc tatttttaga 180 tgtgttccct gacacccagg a 201 <210> 7 <211> 201 <212> DNA <213> Homo sapiens <400> 7 tgcctctgcc aggccccacc tgctccactg cctctgttct gttgcagtga agtgctccgt 60 gtgcaagagc gtctcggaca cctacgaccc ctacttggac rtcgcgctgg agatccgggt 120 acagatctgt cctgcccttc acttttgcag taggagagcg aggccagagg gtgaaacaga 180 acccgcagaa cagtaaaggc a 201 <210> 8 <211> 201 <212> DNA <213> Homo sapiens <400> 8 ggactttatc aaagatggct gactagatgc agctgggaag tgctgtcctc acagagagaa 60 accaaaattt tgactacacc aacataattt gaacagatct ktgatgagaa aacaccaaat 120 gtggatgggg aaaagacaca gttgctgagt cggaagaggg ggaaagctgg gaatcccatg 180 tggagtgccc aaatgctgtg g 201 <210> 9 <211> 201 <212> DNA <213> Homo sapiens <400> 9 actatgctgt ttacaaagca ctttcatatg caggatctca tctgtattca gaggctcact 60 ggtgccctag gcagggatga tgttatcctg gagtaacggc rtaacttagt ctgtgaatga 120 cacaggacac attcttggca actctgtagg acagggcatt tggtccagac aggacactca 180 ccgggctaca aggtctagcc c 201 <210> 10 <211> 201 <212> DNA <213> Homo sapiens <400> 10 ccaatgtctg ctccaatatt ttgtaattga catgtatctg agtctaagag attaaaccaa 60 ctggcacacg acccaacagc atctttggtg attaaaagaa sattggttgt tgcctaaata 120 aaacctgggg ccacgttcgc ccccaggagg acccagtgct aatctcaaat cctgagaacc 180 agtcatttgg gctgggcaaa t 201 <210> 11 <211> 201 <212> DNA <213> Homo sapiens <400> 11 caaattcttc tagagataaa tatttttagt gtcttgaaaa tatattgcca aattttcccc 60 taaaacatgt ataagaatgc tcattttacc atacaatcac ygggcttgaa tatccatttt 120 aagtttaacc agccttaatg attccgttgt actttttttt tttttttttt tgagacgggg 180 cctcactctg tcgcctaggc t 201 <210> 12 <211> 201 <212> DNA <213> Homo sapiens <400> 12 tccaagggga aaaactatct taaaaaataa ttttctatgt attataaaga aagctcgggc 60 ctgttcaacc caacaattct gagttttcaa gtcattctat ragcaggtca accagaaatt 120 gcctgaaccc cctcccatag ccaaaaaact attcacccaa ctggcagaaa gcataaccag 180 cagcttgccc atctcttcat g 201 <210> 13 <211> 201 <212> DNA <213> Homo sapiens <400> 13 agggagaatc tacaccagga aaccataggc tcctgaggtt gaatgcaagt tgcgtgtgtt 60 cctatgtgca aagagaagcc atagctatca ttttctgagg ygtccaagac ccacaaaaag 120 ccaaagactg cactacccga gagactgcag caggaatgag tggattaagc cattcagcat 180 gtccagacat acaaaatcac t 201 <210> 14 <211> 201 <212> DNA <213> Homo sapiens <400> 14 catcgtgagc aatgtattta aggcctccca aaacaaaata atattagcat gacgtatatt 60 tggttaagtg tcataagtat cttaaagcac catccctttc maatctcctt tacagaacat 120 cactaagctg acctctgtat tacaaggcta agaataataa gttttaaaga gtgacaattt 180 tagaattttt cacaatggta t 201 <210> 15 <211> 201 <212> DNA <213> Homo sapiens <400> 15 tgccttttat aagttatgga acattaacat gaaatacata tagaatggaa tttggtagct 60 tgcattacat aaatttattt tggcgagtga agcccatagt yctcaaatcc gattcataaa 120 attaaaacct cttattttct tctggagcct ttaagggctt ttgaaaatca cagttaaaag 180 gtccagattc ttatcgttca t 201 <210> 16 <211> 201 <212> DNA <213> Homo sapiens <400> 16 tttcgaaggg aaaatgattt tatagaaagg gatgggtaac ctttatgata aaattgcttt 60 gctagagcgt gttgcttgtg acagcaccac ctttctgttc ytgacaatgt ttgtcttctt 120 aactaaacaa acgttagctg agttgaatga aattatgtac gaaccagaga agtcgggagg 180 atgtttgagg ctcgagcccc c 201 <210> 17 <211> 201 <212> DNA <213> Homo sapiens <400> 17 cctgtttgta gcccagctac aaacagaaga accaccaagc tgacttgtaa actataacat 60 gtgcttcttc atttaaagct tatttaaagt tgttgaactt ygggttggtt tggttcacag 120 aaatagctaa ccaataaaaa tgaataaaaa attctggtat gttcagaaaa tgaaattcaa 180 agatgaaaat gaacacatta t 201 <210> 18 <211> 201 <212> DNA <213> Homo sapiens <400> 18 gaatatggaa aataaaacca cttttggggt tggggtttcc tcaagccatt cttatttact 60 gagtcggttg cctctggaaa cttttagctc atgtaactaa rcatcgttca ctgccctgtt 120 ctttatgcat ctcagtaagt tccacctgca gaatggtgaa attttgaagt ggaaaggacc 180 ttgatcataa attagttcaa t 201 <210> 19 <211> 201 <212> DNA <213> Homo sapiens <400> 19 tatttaagtc atttgcactt gtgtgtgttt gtaagaactt acgtataaaa tgttcctagt 60 agattttaaa aatgatatta ttttaatatg aaattggcta rtgaagttct agagaattaa 120 tgtttacatt ttgacaacca aattccttat gtactttaca tgtgtttact taaaagtctt 180 acaaaataga atttgccctt c 201 <210> 20 <211> 201 <212> DNA <213> Homo sapiens <400> 20 tgataatgtt ctggcaggtg gcagaaaagc atattgcaga agaggtattt tttctgattt 60 gcacaaaggc atcatattgg atagatgcaa ttgtgagttc yttaactgtt tctttttccc 120 attccttttg cgatacctct ctacctttac tcttctagta tttcctggct atgaaattgg 180 ctaagggcag tggtggcaga a 201 <210> 21 <211> 201 <212> DNA <213> Homo sapiens <400> 21 taactgattt tctacttagc atgctgtttt taaggttcat ctatgttcta gcatgtatca 60 atacttcatt ccttttatgg ctgaataatg tttcattgtc yggctatact acattttatt 120 tatctattta tcagttgata gatatctggg ttgtctccac cttttagcaa ttacaaatag 180 tgctgctata aatatttgtg t 201 <210> 22 <211> 201 <212> DNA <213> Homo sapiens <400> 22 gaaattgatt aaatatggct cttttcctaa gcagatgaat aactctatat tgctcgttct 60 gcatgcctat aaaataatac aatgaacaat gttgacttca kaattgagaa catactccca 120 ttttgctagg tataggcaaa agagaaaaca caagctaaaa cctcaatatc aaggtaatgt 180 ttatagcact atattttcac a 201 <210> 23 <211> 201 <212> DNA <213> Homo sapiens <400> 23 ccttacctgg gagccatcta ctctggaaac catggatacc tacacatctg tgcaaaattg 60 acacagtgcc tcagttattt gggtaaggct gaccagtgaa ytctgataaa ttgctgtaac 120 aatgaccacc catctgtcaa tgtgtcacca agcataggct gtatacactg tgcagactgt 180 aaggatccac tgggctttcg g 201 <210> 24 <211> 201 <212> DNA <213> Homo sapiens <400> 24 tttaaaaaaa actttctgtg aggttcttgg agaagaacct atgaatgagt atgaattccc 60 cttgtgtctg tgacccccag ggtttttaga gactcttgtt ygcttataat aaacctttag 120 caattagtta aaaaatttag cttacttttt cttaccattg tccagtagta tctgtttcag 180 gtaagcaagt gcttgtgact c 201 <210> 25 <211> 201 <212> DNA <213> Homo sapiens <400> 25 gaccttttga catatagggc ctagctgtaa tacatttcaa tgttcagtct ccatcccaag 60 gtgaacatgg gtcatatgtt atatacatat tgtttcaata ygcccgtgtc aggactacct 120 tcatgagtat acatagcact tcctgcaacc tattgaatat gtatgtttag ccagccgggt 180 tggcataaag ctcctacccc a 201 <210> 26 <211> 201 <212> DNA <213> Homo sapiens <400> 26 atagatcaaa atagcctggt ttgttacttc ctcaggtagc tagattatgt ctggattcca 60 gattttgttg tctgaaaagt aagcttctca ttgcttaagt stctcttata ggtttctctc 120 atatgtagcc aagtacaatt catgatgata tagtaaataa aacacatgat gttgtcctca 180 gcaaacctac agttttacaa a 201 <210> 27 <211> 201 <212> DNA <213> Homo sapiens <400> 27 ccgcagcccg gtggctcaga cctgcgaagg aaccaaggca agagggagaa aagccctgcc 60 gcctgatccc acgccgccac tcacagaccc ttcgttgacc sgcagcattg aacaggaaaa 120 aaaaaaaaag atgaaaacac agaaaacccc aaaaacccag acggggagac gatgtgggga 180 agagaacgtg ctgggagcct c 201 <210> 28 <211> 201 <212> DNA <213> Homo sapiens <400> 28 tatgattaca ggaggtacct ggagtagtca aatttataga catagaaagg aggatggtgg 60 ttgccagaat gggtagaatg gggagtggtt atttttcatt yttctgagat gaggtctcgc 120 tctgtcaccc agggtggagt atggtggtgt gatcatagct cactgcaact tcaaattcct 180 ggactcaagc aatcctccca c 201 <210> 29 <211> 201 <212> DNA <213> Homo sapiens <400> 29 gtgtacttca gtgggttttt gtagtggctg gtaatgatct ttccctatca tatttagtgc 60 accttttagg acctcctgta aggcaggtct ggtgataatg mattttctca gcatttgctt 120 gtctgaaaag gatttttatt tctctctcac ttatgaagat tggtttggct ggatatgaaa 180 ttcttggttg aaaattattt t 201 <210> 30 <211> 201 <212> DNA <213> Homo sapiens <400> 30 acctttccct tctgttaaca cggcggtaat ttattacata agagatgtta atcctgggga 60 gaaattctaa atactcaggg aataagtaat ggctgggccg yaaatgatga aaatgtgaat 120 gtgttacata gattctgaat tattcctggc attccctggg gagagagaat agaagtaagt 180 tgcaatcagt tgtgatacct c 201 <210> 31 <211> 201 <212> DNA <213> Homo sapiens <400> 31 ggctgccgtc aaaagtgcat ggacgagtaa agcctggcat caccagggaa tgaaaaaccg 60 cacagtgaat gacctcggcc tggcagtccc acacttaaaa mtcgattgtg aaggcatgct 120 gagaaaggca ccagatgatt tgtgtccaga cctgttcgct ggacggagtg aaaaggtgtg 180 caacacataa agggccggcg g 201 <210> 32 <211> 201 <212> DNA <213> Homo sapiens <400> 32 atgaaatcat tttaggctgc tattggtcat ctataatatt tttaaaatct gccaaagatg 60 tcaccaaaga aggttccatt gtatattatg tgtaacatga rggaattaaa caaataaaat 120 gaataaagtg tttatacatg aaaaaatatc aaaagtgtgc atactggata cctgacttcc 180 atcccaagaa taatttcctt c 201 <210> 33 <211> 201 <212> DNA <213> Homo sapiens <400> 33 aataattagt gttcataaca tttggaattt cagtatgttt aaattcatat tatgagaaga 60 tcaacaggct tattatgttt gcataaatat tagtataggc ygcttttatt atagaataaa 120 gaagaataaa cattcttttg tcttttcaaa atacagctat gcacatacac atgaacacaa 180 aactatcatt tacaaattat t 201 <210> 34 <211> 201 <212> DNA <213> Homo sapiens <400> 34 agttcctgcc ctccagttgc tcacagtcta gcaagggatg gaggagacta attaagaaac 60 cttttattac agcacagctg actgcacgaa ccaaaggaga mgcatgagcc agagagacaa 120 ggaaggcttt caaaggaagg gatggtcaag ctgggtttcc aaggatgact aggagctggc 180 caggcagcaa agggcattcc a 201 <210> 35 <211> 201 <212> DNA <213> Homo sapiens <400> 35 acctcctgct gtgtggcccc gttcctaaca ggccacggac cagtaacagt ccaaggccca 60 ggggttggga atcctgcctt aaggcgcaga gcagttacat yatggcactg aagtttatac 120 atcagtttct tgaaagtttc attatcatgt gtctttcccc aggactgacc agctctcagc 180 acaacttttt aagaaaatga a 201 <210> 36 <211> 201 <212> DNA <213> Homo sapiens <400> 36 aatggctaaa tccatgtcaa aatgtgcaga ataatataat cttatactgt ttcacctatc 60 aaattagcaa ataattttaa aagttctatt cctcatagcc rgtgtgcata tgctgagaga 120 agtccttttt tttcctgtgg gaagcttaat tgataggaaa ataattaatt gaaaaataat 180 ttgacagtat gtaccaattt t 201 <210> 37 <211> 201 <212> DNA <213> Homo sapiens <400> 37 ttccaatttc tagacttttc atgaaatatg ggaagggtgt aaccagaagg actactacat 60 ggtaccttta ggccttgact gtcagtaccc ctccatcagc rtgagtcttg ggcagagctg 120 ggcatcagtg aacagacaca gtgaccaggt acctggcctt cctcacccct tgctgccctc 180 tggccctcaa agccttgagc c 201 <210> 38 <211> 201 <212> DNA <213> Homo sapiens <400> 38 tggaacacag gttctttctg acctgggtcc ttatcttctg ccatttacct cttggaagac 60 ttacgttgta ctgacgctgg actacttgac atttcctatc saagttgtgt ctccaggccc 120 ttatctatgc tgctcccact gcctggaata ccctttccct ctgccatgcc caccaggtga 180 atcacagctt atcctttaag a 201 <210> 39 <211> 201 <212> DNA <213> Homo sapiens <400> 39 ctccacttac tggctattct ttggtttctc tcctctcctt gagccttcct atgccctcag 60 atacaacagt attgaaattt gatcaattag taatcctata rtggtctcta agtgttcaac 120 tgaaaggaaa agttgcgcat ctttctttct ttaccgagac agggtctcgc tctgttgccc 180 aggctagaat gcagtggcgc a 201 <210> 40 <211> 201 <212> DNA <213> Homo sapiens <400> 40 tattttgcat gtaagaagga caaaaatttg ggggtgctgg gcagaatgtt aatgagtgaa 60 tatgttctag aaaaagcgca ttgaaggaga gaaaaatgtg ygagaaagag accaatccat 120 ggtgaaaagt cagtggttta cactccagag aagaactaat cagctctgtt tttatatagc 180 ataagtttaa catgctggga a 201 <210> 41 <211> 201 <212> DNA <213> Homo sapiens <400> 41 caccgcacct ggccccctag caggttcttg atagttgctg acaatggagc tagctgggga 60 ttctttcctc cgatggtcat tatgcattat agacaaggtt yctgtgttct cattatgccc 120 ccaaggaaca tgcttcagca aacgtgaaaa atgccagagc catacatttt tttttttttt 180 tttttgagac agggtctccc t 201 <210> 42 <211> 201 <212> DNA <213> Homo sapiens <400> 42 ggtcacaatt gtgcctctgt gcaggcatgc ttgcgcccct agccttctag tgtttatcct 60 tgctgatctt ttgatttctc tcacagaacc ttggatacct ygtttcccat ttcctggtga 120 ggtcaccacc ctctccggtg gtggcgctgg gccctgatct ttgctgtttc tccaccccat 180 gtgttctgtt tcgcttccat t 201 <210> 43 <211> 201 <212> DNA <213> Homo sapiens <400> 43 agacggggtt tctccatgtt ggtccggctt gtctcaaact cccgacctca ggtgatccac 60 ctgccttggc ctcccaataa catccctact ttaggctaca ycatatataa tgagtttagt 120 tggttaatgg ctacccaaat tcaagtagta agcaaagtac ctttatgcct tgagaggcat 180 gaaaacagca gcctccaggc t 201 <210> 44 <211> 201 <212> DNA <213> Homo sapiens <400> 44 gttcccaagc aggaagctgg ggcgtgatta aatggatgcc ggacaaccaa aaaagcaaaa 60 gcccgcttca cagccacatc cagtgtctaa atccacatca yctaaaagta cctggaagat 120 cataggcttc ctcgtcaggt cctccaaggc cacttccatg atcctgcttc taggactggg 180 accccacccc cttcacacgg c 201 <210> 45 <211> 201 <212> DNA <213> Homo sapiens <400> 45 tagaatggga gacagatttt ccctgagtgg ttcccagctt gaaagggcct aagatatttt 60 cctttcacaa gaggtatgcc cgtaatacct tgaagaactt ygtgtaacaa ctaaataaat 120 aaatggtaac aaattagcac tcaataaatg tcagctatta gcttttccaa ataatcctaa 180 aatgtgcaac ctcttgttta c 201 <210> 46 <211> 201 <212> DNA <213> Homo sapiens <400> 46 tggtcctcat tctgcacctt gctgttctgt tctatgtaac atccaggctg ggaggggagg 60 gggccggccc tcctcctctg tcccaggctc tgcagtgggc racttggttc cgtccttacc 120 tcctcagctg ggcatgtgat cttggtgctc tgagccttgt tctctgtgct aagtatatgg 180 ggttcattgg aaaaactgac a 201 <210> 47 <211> 201 <212> DNA <213> Homo sapiens <400> 47 aaggatgaga tcaggtatgg tcagcatccc tcacctccca aatcctcttc caagtcattc 60 ctcttgcacc cttgtgtgaa aacccttcct cctttgagag rctatcaatc tggctctatc 120 acagtgtcag tcaaaattcc cttggatgta aacaacagaa actggctggc tgatgtagcc 180 tgaaaatgaa tgtattcaaa a 201 <210> 48 <211> 201 <212> DNA <213> Homo sapiens <400> 48 caggcccatt ttgcagaggg gaagactgag gtgcagtgat gcaaaatgtg tggtggaggg 60 ctgggcctgg aatctgggag ttctggttcc gggtgaccgt mcactagaaa gggaaaggtg 120 gcagaaccat atatatgagc ctgttacttg ttcaaggact tggtcagggg cctcacagaa 180 cttggaaaag agcaacggac t 201 <210> 49 <211> 201 <212> DNA <213> Homo sapiens <400> 49 catgtgttcc ttatagttca tccatccaaa aaaattgcag ttcctcaatg ttacactctc 60 ttggtctgtt ctcttagtgt aatcttcccc atacacattc yttgaccaaa attaaccttt 120 aatacttagc tcactttggg aggccaaggc aggtggatca cttgaggtca ggagttagag 180 accagcctgg ccaatatgat g 201 <210> 50 <211> 201 <212> DNA <213> Homo sapiens <400> 50 ccactcccca agccaccagg tggccctgcc cacacctgga ttcatttaac cccatgagac 60 cgtgtcggac tcctgccctc cggaattgcc agctaataca kttgtgttgt tcaaaccact 120 gaagttcatg gtcagatgtt atgacagcag aaatagcctg atacactgtg agaaagtgga 180 gagcacacga cgcctcggga a 201 <210> 51 <211> 201 <212> DNA <213> Homo sapiens <400> 51 gggagctagt taggcaatta gtacagtcgt tgagaaaaca ggtaatggta gcttaaacta 60 acaggaggat aaaggagaag agaagtacat gggttttcaa yacatctaag aggtaagcta 120 gcagggtttg gctatcaatt gggcatgaaa agtaagggag gggaatgtat cataagagta 180 acgtctcggt tttagagtag a 201 <210> 52 <211> 201 <212> DNA <213> Homo sapiens <400> 52 caagtgaatc actaatgaca tttgttggtt tattggttga aaagtacttg ctgtagataa 60 actatccacc aggccatgtg ctcttcttca cctcagaacc rtgccttagt ttatcactag 120 ctgcctcctt ctctttcttt atatcctagc ttcaatggca gtctttcctc atcactttct 180 ctaattaaac cacctattct a 201 <210> 53 <211> 201 <212> DNA <213> Homo sapiens <400> 53 acaagtctct aaatgaggta cgtaagttat tactccagac atcagggagt attttgttta 60 tgaaacatct ccaatttatc actagctggt tatcattatt ytcctcataa atctatagat 120 gctggtttta ttttctataa gccatcctta gccaaggaca tcccattatg acctttccct 180 agataaggac tccattccta g 201 <210> 54 <211> 201 <212> DNA <213> Homo sapiens <400> 54 tataattttt tagaaatagc tgtgacatga aatatggcct tgacagagaa tgaagaacat 60 atcaagaaca acaaatgacc aacatgaatt gtctctgata ygctatttca tttacctgtt 120 tatgaaatgg aatatttcta gtgctcttta tcatcaaatg caaatggaat atgtgaggag 180 gcctggcagt tccaccagga t 201 <210> 55 <211> 201 <212> DNA <213> Homo sapiens <400> 55 agaatcttga agatttacct gttcccatag gtactgcagc attattcata atcattaaga 60 tatggaaaca acttagatgt ccattgacag atgaacgaat raagacaatg tgatatctat 120 ctatctatct atctatctat ctatctatct atctatcatc tatctatcta tatcatctat 180 tatctatcta tctatcatct a 201 <210> 56 <211> 201 <212> DNA <213> Homo sapiens <400> 56 aggtctttac aatttggcat gtttttgcag tggctggtac cagttgttcc tttccatgtt 60 tagtgcttcc ttcaggagct cttgtaaggc aggccttgtc rtgaaaaata tctctcagca 120 ttttcttgtc tgtgaaggat tttatttctc cttcacttat gaagcttagt ttgtctggat 180 atgaatttct gtgttgaaaa t 201 <210> 57 <211> 201 <212> DNA <213> Homo sapiens <400> 57 catgagaccg tgtcggactc ctgccctccg gaattgccag ctaatacagt tgtgttgttc 60 aaaccactga agttcatggt cagatgttat gacagcagaa rtagcctgat acactgtgag 120 aaagtggaga gcacacgacg cctcgggaaa acacctcctt ggctgggttt tgctaaagca 180 aaaatagaaa tccaatttag t 201 <210> 58 <211> 201 <212> DNA <213> Homo sapiens <400> 58 ttcctggagg tgaactctta ctcatgctat agaactcttc ccccaattcc cccgctctgt 60 gagttatccc atcataagac agacgcaatc tcaaatttct stattcattc tccaacagtt 120 atgacaacgg ccagcattca ttgagcatgt actaattgcc agacactatt ctaagctctt 180 tacacttttc tttctctctc t 201 <210> 59 <211> 201 <212> DNA <213> Homo sapiens <400> 59 accaaggttt ccaaagctgt tgaataaatg aaaggtaaat aaaaatgcat tgaaccccaa 60 aaaagctgct gaagggaatt ttcataatgg aagggaagta ytttttgctg aagggaatct 120 ttacaaaagg aagcattttt gatgcttgtt tttaagagat atacgtatat atacattaat 180 aaatacacat atttacgtta a 201 <210> 60 <211> 201 <212> DNA <213> Homo sapiens <400> 60 tgctcttctc gaggagtatc tttgtggtgt tctctgtatt tcctgaatct gaatattggc 60 ctgccttgct aggttgataa aattctcctg gatgatatct kgcagagcgt tttccaactt 120 gtttccattc ttcccatcac tttcagctac accaatcaaa catagatttg gtcttttcac 180 atagtcccat atttattgga g 201 <210> 61 <211> 201 <212> DNA <213> Homo sapiens <400> 61 taaaaaatag gagaaaatct ttttgacctt gtattaggct aaagattatt agatatgatg 60 ccaaaagaat aatctataaa agaacaaatg gataaattgg wcttcataca cataaaaaac 120 cttcagctcc ccaaatgata ctgttaaaaa aaatgaaaag acaactacag gctggaagaa 180 aatacttata aagtgcatgt c 201 <210> 62 <211> 201 <212> DNA <213> Homo sapiens <400> 62 tttttttgtg ttcttgtttt ttggagcatt aaaagacagc acttcctttc tactatatga 60 caacccttca aatcaatgaa agagctgtta tgattgtcct rctatgatcc taagttaaac 120 ccatgagttt tcctcatctg ctcaacatgt ggtattgcct tcagaatctt cactagtctg 180 gtcactctac tgttgataga a 201 <210> 63 <211> 201 <212> DNA <213> Homo sapiens <400> 63 cccatgagtt ttcctcatct gctcaacatg tggtattgcc ttcagaatct tcactagtct 60 ggtcactcta ctgttgatag aatcaacctg ttcgtgattg ycctaaaatg tgattaccca 120 gggagggatc acttagtttg ggctgcagtg ggactatgaa tcctgtgttg aaattacaaa 180 ctacttttat tggcctggcc t 201 <210> 64 <211> 201 <212> DNA <213> Homo sapiens <400> 64 ccctcacctg ccgtgcctga cacccgccag caacacacac ttgggaccag tcctgctgcc 60 ctgtcacccg gcatggctga ccctgaccgg ggccttttcc ragctgctgt agctcatctc 120 agcccaatgc cactgggaga cattgcagca catctctcac cttcgactgt ggaatatttg 180 aggacaggcc tgtgactcac c 201 <210> 65 <211> 201 <212> DNA <213> Homo sapiens <400> 65 ttcatcatac ccacccagat ttttagccct gtgtgtgcat acctgttgga aacaaagacc 60 acatttccca gctcccatgg agctagatgt tgcaatgtga mtaagttttg ctcaacgaag 120 catgagcaga ggtactgggt gacttctagg aagtgtcctt taagggtggg gcacaacctt 180 ctgcccttcc tccttcttat a 201 <210> 66 <211> 201 <212> DNA <213> Homo sapiens <400> 66 taatatgagc caagtttttg ttccctgtgt caggtactga cacagtggca ctcagtgctc 60 tactacagtt ggcttatttt taatcatttc aattatcctc rggtagaaca tcatccttga 120 ctgagagaac aggaaactga ggacaacaga cgtttgaaaa tgtgttaatg tttcacagat 180 aatggcagag gacccctgga t 201 <210> 67 <211> 201 <212> DNA <213> Homo sapiens <400> 67 ggacataata ttagacatag tcatagaaat ccttaataaa atattagcag atagaattaa 60 tcaatatatg aaaagtgtat ggtgtataca tgatcaaggg rgttttattc caccgatgct 120 tgatatttga gaatcaatgt acaatcatga catagtaaac ataacccacc acagtaacag 180 gctaaaggaa ggtaatcata t 201 <210> 68 <211> 201 <212> DNA <213> Homo sapiens <400> 68 gcctcaaagc tcctgcaccc ccagcacttg ggctgaccaa agagaacagc agggactttt 60 cttgtgtgtc acccaaggaa gaaggaagtg acaaacaatg rccaaagata ggggtggaga 120 ccttaaatgc ccacaggggc caacaggtat tgtaaccaag tggcaaggcc agctgaagac 180 actagggagg ctgaagacag g 201 <210> 69 <211> 201 <212> DNA <213> Homo sapiens <400> 69 agttattcat tctgtataac tgaaattttg tactctttga ccaacatctc ctcatctctc 60 cctccccaca gtccctggca atcaccattc tactttctga ycttatgagt ttgacttttt 120 tttagattcc tcatgtaact gagatcacgt ggtctttacc ttcagtgtgg agaaaaggga 180 acctttttac atggttggtg g 201 <210> 70 <211> 201 <212> DNA <213> Homo sapiens <400> 70 tttataaatt atccagtctc agggaaattc tttatagcag tgtgagaatg gactaatata 60 aggggcaaag agaatcattc ctggacagct ctgtagactg ytgcaagaac tattccagtt 120 gaagacaaat gtgtgactct gccctgctgg tgagctttgt tttctctcct atattcatcc 180 aatgaatctg acgtctaggt t 201 <210> 71 <211> 201 <212> DNA <213> Homo sapiens <400> 71 tgggctttcc tccaagtgtg aaaccctgga tgcgttctga aatccccaag gatgctgaga 60 gccacagacg tgtagacgga aagaaatcaa accattcgcg ytgctgatgg tgggaggaag 120 tgcgctgcag cccgcacctg cctcccctga tgccaacagc aggaccggca ccctcgttct 180 ctgcagtcac actccccatg t 201 <210> 72 <211> 201 <212> DNA <213> Homo sapiens <400> 72 tggaccagaa aaagaaaatg aggtgacaga caaatgtatc atctattttc agtgaagagt 60 tgctccctcc aggaaagcca tttgtgatta tttaattgcc rtgaaatttt cctcaggttt 120 aataactagc atgcagggaa aatcatttat tacatgaata cttgcaataa tcaaaatata 180 tttagaagat tttaataatt t 201 <210> 73 <211> 201 <212> DNA <213> Homo sapiens <400> 73 ataatgtttc catggaaaag tctgcttcca ggcttattga ggctgcattg catgttattt 60 ctttcttttc tcttgtgctt taggatcctt tctttatcct ygacctttgg aagttagtga 120 ctgttagttg ccttgaggta gtcttctttg ggttaaatct gcttggtgtt ctataacctt 180 cttggagtta actgttaaca t 201 <210> 74 <211> 201 <212> DNA <213> Homo sapiens <400> 74 ccccgagtcc ctactattac accaggtctc ccctgcctag agaagtgagc cttacagctg 60 aatgcacatt tcatagaaac caagaggtta ctcttcattg ycgaagtgaa gcattagtct 120 tgtaaaatta aaaaaaaaaa aaacaggcca tctttgagtg aataatgaga tacttgcctt 180 aatttgattc ttaattataa t 201 <210> 75 <211> 201 <212> DNA <213> Homo sapiens <400> 75 acatttgggt tttgtttcca tatggtggtt attgtgaata acgctgcaat gaacatgtga 60 gtgcagatat atctacaagt actactttca tttcctatgg ktgtatatcc agaagaggga 120 ttgctgaccc acatggtagt tctattttta atttttcaat gagcctcatg ctctgtcccc 180 taatggctgt tccaatttac a 201 <210> 76 <211> 201 <212> DNA <213> Homo sapiens <400> 76 catttaagtg gaagaggata atgtgtcatt gatcttgagg tagttggtaa aagtgagaga 60 gaaaaataca ccgtaggaaa accaaacaaa acaaaactgg rccatttagc ctggcaggga 120 cagaaataag gagaccctta agagaggagt ttgaaatcac agtaaaaagt gcaagtgatg 180 tgatacaata gaaaacacgt t 201 <210> 77 <211> 201 <212> DNA <213> Homo sapiens <400> 77 gggagagcta gccttaaaat gtaaccgaga ttaagaaagg cagaggaaaa acaaaagaaa 60 aaaatataaa caaaagaaag aaatgacaac ctcattgtaa yggtaaatca agtcaaaatg 120 gaagccagag gcaccagtgg gcttttaaaa ttacgtaagc taataatttc cctttattgt 180 taagccagtt tgagttggct t 201 <210> 78 <211> 201 <212> DNA <213> Homo sapiens <400> 78 ccaaggacag agcactgaga ctgtaaagga ctaggagaca ctgatcacta tggggagggg 60 atatccctgc atgcaggaca acaggaccca ggctagatac rggtaaatgc agatttcctc 120 tgctactgac actgtttaga taccgtgaga cattctgagt atgaagttga agctagtagc 180 aaactactca aagattaaat a 201 <210> 79 <211> 201 <212> DNA <213> Homo sapiens <400> 79 aaaaacctat gagaatattt tgcagtgaga gtttagtttc atttttgttt actttgcttt 60 tgcatcaata atatcttcaa gagaagaaac attagacaga kttttagtag ttaggtcaac 120 tcctatcagt ggttttcata cttttctttt tttccggatt cctttgtgaa agtaaatttt 180 ctgatgttga attgttttca g 201 <210> 80 <211> 201 <212> DNA <213> Homo sapiens <400> 80 gcagtccaca gtgtttacag agtgggacta tatacagtca cccttctctc acccgtcctc 60 cctgctctga gacacacccc tgtggcgagc accgcagaaa ygggaagcca ctacttaaga 120 tcggaagtta agagagctcc ctccgaagag aaaattttta tactaaaatc tataatttaa 180 ttcaagagaa tgcttttatt t 201 <210> 81 <211> 201 <212> DNA <213> Homo sapiens <400> 81 aagccaccat ccctggccaa ccgtacatac ttttttaaat gtatcagagg aaagaaacag 60 gacacaggtt ggggatagaa tctagctttg tctgaatgta mcttgttttg gaaccatgta 120 aatattttac atacttagta aaatacattt aaattttgaa aatgtaccct ctaaaaactg 180 aaagcagagc aaatgtattg a 201 <210> 82 <211> 201 <212> DNA <213> Homo sapiens <400> 82 ccactttccc tttgcttttg aggaacattt cagaaactat gttcaacaaa tactactgaa 60 tttgtattga attggccaag acaataattg aaaccagaaa kaaagttttt cattgggaaa 120 tggtttctac taacaaattt agtatgtcca cattaaaaaa ggtgagagat tatatcacct 180 tctctagatt gctacttttc t 201 <210> 83 <211> 201 <212> DNA <213> Homo sapiens <400> 83 gggtggactt tggggagtct gcatgctctc cagctagtgt tgcctgtggg gagcaggttt 60 gcaaggtttg gggagcattt tggcagcttt ggagagaaca ytgaagaagg atggaccctt 120 aaggcccaag ggagtgattg gtagagcctc tggagcagga ctgggcctga gatgtgggct 180 ctggaacttg atgctagaga g 201 <210> 84 <211> 201 <212> DNA <213> Homo sapiens <400> 84 ccacgagtgt ccgcaggtgc acagaaacat gggcagtggg atgtttccat gggtcaccta 60 attccagcca aggtggacaa accttcctga acagaatggg ygttgtcagt gtggagaagt 120 atccacaggc tatggccgca gaagctgctg gatggctgag aggcgtctcc aggaaataaa 180 tggggtgcct gttagatagc a 201 <210> 85 <211> 201 <212> DNA <213> Homo sapiens <400> 85 cacatcaaat catctatcaa ttctttctcc atctctcaag cccaactctc ccttgccctc 60 tccagaccat gtgtgcatat cacctgggtc gtcttcattc yctaaatcac ctacgccttt 120 tccttggctt tctcaatttc ctgaggcaca ttcttcaaga gcttgctaag taaagaccca 180 tggagaatac acttttagcc a 201 <210> 86 <211> 201 <212> DNA <213> Homo sapiens <400> 86 agtggcaaag tcactttgca gagcagtgtg cagaaaatta tctgcatctg aaaaagaaca 60 tattgggagt tttattcaga ttgagctgga tacataaatc rtcttggact gaattaacat 120 cttaacaata gtggattttc taattcttga ataccatata tttgttatat gttttaaata 180 tttatgtttg aaaagttttg t 201 <210> 87 <211> 201 <212> DNA <213> Homo sapiens <400> 87 cctttatata gaatgcttat aatagtattg cttatattgt gaaaaaagtt aactagcaga 60 ttgaataaat aaatccatgt gacagggaat tggcagccac raacatattg gtggtagatt 120 aatacataat atataataac atttaattat tttgtatatg gcttactaaa atatataagt 180 ataattaatg acataatgat a 201 <210> 88 <211> 201 <212> DNA <213> Homo sapiens <400> 88 ttttggaata aattggcagg gctcaggaat gtggtagaat gaagaagata agagaattct 60 tgcactctct ggaaaagctt tcagcacaag gagaatggag wttagctttc cctatactgg 120 atgaccctca gtaataatta aggtatttga atgttctgtc cttaacacct gagcttgata 180 aagaacctac tttcagttct t 201 <210> 89 <211> 201 <212> DNA <213> Homo sapiens <400> 89 actgtgaggc accacaccag ccctgggctg cttatgtttc tattactacc tgagaaaaat 60 aaaactctat ctgatttgag tcactattgt tttggggtct yggttatagc agctgacctg 120 tatttaaatt aatacacatg gacacagatg aagcctagtg gaggcttcta agatacaaga 180 tgggggcttg tgtttggaca t 201 <210> 90 <211> 201 <212> DNA <213> Homo sapiens <400> 90 gccaagtaga agctaaagtt ttctcatctc ctcctcttct ctttctctat cgctctttca 60 tgatgcaagt gacaactaat taaataaaac tatctgtgaa wtacatgtgc attgagacct 120 cccagagaca aagatgcaac cttctgccag ccccaaatcc aatctctgct gttccctgtg 180 cccaggggaa cggacccaat g 201 <210> 91 <211> 201 <212> DNA <213> Homo sapiens <400> 91 aaaactctca gaaatgctgg ttaacatata atggacatcc ttttacatat aaatttctag 60 gggccaaaaa aagaagaggg aactgaaaac ctaagtggca rttgtatcca ccctttaatt 120 tcacttgggg cagagaagat aaggtctgtg ccaagtaaag acttggaact gagagcttcc 180 tccccaccaa ccccattgca t 201 <210> 92 <211> 201 <212> DNA <213> Homo sapiens <400> 92 gtggaagagg aactctggaa gcaaacaggc tttagcaaaa gtgatgtaac caaaatggaa 60 tcagatacag attggggaat ctcatcaaca tttacctgta ygcttaaccc agttgtgaca 120 gttagaaaca tgatagttgt ggtgtctggg ggagggtggc atagtggagg ggttgagggt 180 gtggcctctg gagccagggt t 201 <210> 93 <211> 201 <212> DNA <213> Homo sapiens <400> 93 tttgaatgtt ctgtccttaa cacctgagct tgataaagaa cctactttca gttctttgat 60 ctgtgtgtaa cccagcaatg cctctcatcc ctagtgttca mccgagttta tagtctttgc 120 cagagaaaag aaagcatcat tagagaaaca ggccaccagt ttcttctcct gacacttgga 180 tacttcacaa tgtgagttaa a 201 <210> 94 <211> 201 <212> DNA <213> Homo sapiens <400> 94 aaaccaactc ccctggtgct ggaatggttt gtattgtacc atagcatatt atgtggctta 60 tttctaaaat agttagaatt taaatgaatc atgaaaatgc rattaaaaca cactatggtt 120 acaaagattt ttttaaatct aaaacttgga tcttatattt aattgatgat ttgtcattct 180 gtaattttta tattccttgg c 201 <210> 95 <211> 201 <212> DNA <213> Homo sapiens <400> 95 ctcttcccac ttagatttct ctttcattgc ctcatttggc ttcttttcct ctcttggtgt 60 ctctgtgcta acccacttta tttcacttta cactttcttc rgcagcagtg ccatccactc 120 ccatcccttt cttctcttgc cttctctgtt ccttttctat caatgtgctc agcattcctc 180 ctgctcccac taaattggcc a 201 <210> 96 <211> 201 <212> DNA <213> Homo sapiens <400> 96 agtggaagac aagtgttgag acaagccaaa ggttgcgaca aaggcgtaga aaccatccac 60 cttgtcaaat gggctctcat ccttttcaaa gtggagccat kccatgtaga gcagacactg 120 caagcttgat gggaatgagg catatctggc tcaaaagcat gtttatttgt gtgtttttaa 180 aagtgtaaat attgaaccaa c 201 <210> 97 <211> 201 <212> DNA <213> Homo sapiens <400> 97 agggactttt tcactctggg ttagatcatg aaagttaaag tattgggttt gaactgcata 60 aaaaaacaaa caaaatgtgt gtgtcatgat tctagattgt sctaacctat ccagcaagtt 120 caaaactgtg aactattggc taacagacaa gcatgagagt atggctggat aaatgctaga 180 tttatatcat ttgagagaaa a 201 <210> 98 <211> 201 <212> DNA <213> Homo sapiens <400> 98 atattggtac agctttctga atatataaaa gtatattaat aaaaatagag agctgagttt 60 agctttcttt ttgtgacttt tatatttaat aactccaatg watttgatga aacacaaata 120 aatcagctca gaagaattta actgtaatac gtatgctaat attgtttgca ttcaatctgt 180 aagggaatca gaaaccgaag t 201 <210> 99 <211> 201 <212> DNA <213> Homo sapiens <400> 99 agtttggaaa tattacctcc atttttcaga atagtttgag taggattggt atttcttctt 60 ttttatatgt ttggtattac ttcttttata tgtttatcaa wgaagccatc aagttctggg 120 cttttattta ccttgagact tttattagat ctttggtctc attacttcac atgagcctgt 180 tcaggttttg gatttcctca t 201 <210> 100 <211> 201 <212> DNA <213> Homo sapiens <400> 100 ttatatgtta cgttttctac tatttaaatt tcaggcactt cagtggactt caattcatca 60 actcttctac aagagcacgc ttactttctg acactgacct saatcttctt ttcctttgtt 120 agagaataat taaagcctca tatgtagaag cagggctgta aagtcacact gctaagagta 180 ccaatcttgt gactgcagct g 201 <210> 101 <211> 201 <212> DNA <213> Homo sapiens <400> 101 ccagataggg ccttgtagtc cttttaaaaa ctctggcagt tattccagtt gaaaaggtga 60 gcctctgcgg ggttctgatt aaagggttca ctctagttat ygtgtcaaaa tagaaaagaa 120 gcaaggaaga gtaaaagaag gcagaccaat gaggaggtga ttggagcagt ccaggcaaga 180 gtgtttgagg gcttggagca g 201 <210> 102 <211> 201 <212> DNA <213> Homo sapiens <400> 102 aagaacagtt gttttcttta tcttcccttt gagtcctgtt cgaattaaaa tgtatgtttt 60 acaagcattc aaaaaggtaa tggattgttt cacaagtaaa ktcctaagtg ttcagctatt 120 tcagctcttc tttgccattt ggggcttctt acttgttagg tgatttctcc ggccttctat 180 caagcatgat gtgtgtcttc c 201 <210> 103 <211> 201 <212> DNA <213> Homo sapiens <400> 103 ttctctacta agacaactac aatcatatat ttgtgtggaa ttacatatct acataagtgg 60 aaatttattt aatgtcctta catattgtct tgttcattag ytgtctttga aagtcatttt 120 aaaaatcttt gtattacctg cctcaaaagg ttgctaggaa gattggataa aataataaat 180 ataaagcagt gaaatcaatg c 201 <210> 104 <211> 201 <212> DNA <213> Homo sapiens <400> 104 tcatctcttt cgtgtttcta cttaacatta aaaatatgga atacagctat aacaactgtt 60 ttaacatcct tgttggctaa ttctaacatt tctgtcaggt staagtcagt ttggattggt 120 ttttatgttt ttcttctatg ggttgtgttt tcctgctttg catgtcttgt agtctttcat 180 tagatggcag gcactgtgaa t 201 <210> 105 <211> 201 <212> DNA <213> Homo sapiens <400> 105 ggtcacagaa ataacaaggg acttctgtag atcactgcaa gaactttagc atttaccata 60 aatgagattt ttaaaaccac tgaaagcttt tgcaagtaca rgaaaggcat gacctgattt 120 gcattttaaa aaatcatctg gcttctgtct tgaaaataaa atgtgagata aatcggggag 180 accggttagg aggttattgc a 201 <210> 106 <211> 201 <212> DNA <213> Homo sapiens <400> 106 aactcctcac ctcaagtgat ccaccttcct cagcctccca aagtgctggg attacaggcg 60 tgagccactg cactcagcct gtcatctccc atttgcttgt rtaaacgcct gaggctgtgg 120 taggatcctg ccctaaggat agcaattagg gcttggctgc aaggaaggcc cacaggactc 180 aaaatgacaa tgtgtacaca c 201 <210> 107 <211> 201 <212> DNA <213> Homo sapiens <400> 107 aagttctagt tccagtggaa aatttggccc cttggaacta tcagcaacca gcacttcagt 60 catagacctg gctatgttta ccttgtgctt gctttgagtc ytgttgaagt cagttgggaa 120 cacatcatag gtccatcagg attctatgct cgggagacat ggcaagccct atgtgagaag 180 ggtggcaagg aatggcatac a 201 <210> 108 <211> 201 <212> DNA <213> Homo sapiens <400> 108 ggaaatgatt ttgttctttt ttatggctgc atagtattcc atggcatata tgttacgtac 60 cgcagttttt aatccaatcc accaccaatg ggcatcagaa ktgatttaag tctttgctac 120 tgtgaaaaac atatgagtac atgtgtcttt ttgatagcat gatttatttt tctttgggta 180 gatatccagt aatgggattg c 201 <210> 109 <211> 200 <212> DNA <213> Homo sapiens <400> 109 aagcactggt tgacttttgg tgggcaacct gaaagagagc tgtgaatgac atctctcctc 60 cctgctccta actagagagt gtgtctcaga gaactgtgcc rtttaagagc cggaaggcac 120 tctcaaagcc acctggttca atatttccca aagaggagca ttttctgttc atacaatagg 180 atattatttt agcttatgca 200 <210> 110 <211> 201 <212> DNA <213> Homo sapiens <400> 110 cctcctaaat caaccttaga cccacattag ctttcacctg gtgtgactgc tttagttgcc 60 tgttgtctgt gctgctgtcg ctttctccct actaaagcca ycctctgttt tactacctga 120 ttaacctcct ccaagcacac acctaagcac accaccctcc catttacaac cagcaggctc 180 aaaacctttc agtggctccc a 201 <210> 111 <211> 201 <212> DNA <213> Homo sapiens <400> 111 tgctggaggc agagggtgcc aggatgcagc tgtgagccag agaatgccaa ggattttcag 60 ccaccccaaa agctaggaag aggcaaggaa gatttctacc ktgagtttct gatagagtat 120 ggcaatgctc ttgatttggg acttctagcc ttgagaattg tgaaataata catgtatatg 180 ctttaagccc ctccaatttg t 201 <210> 112 <211> 201 <212> DNA <213> Homo sapiens <400> 112 caacacgacc tccctcacat ggctgggggt tgatgctggc tgcaagctgg gagttcagct 60 gggcctatca ggaagggacc tgaactcttc tctatgttga yctctccacg tggctacttg 120 ggcttcctca cagcatggtg actgagttct aagaagaagc actccaagag gcaaaggctg 180 gagctgtgtc atttccgcca t 201 <210> 113 <211> 201 <212> DNA <213> Homo sapiens <400> 113 cttaaataat tctgtgatcc tggctcccga taagaggaaa ttgtctttcc aaaaggcata 60 atagcctcct agggatttgc tttcctttga acaatgaaga rggaggaaaa ggtgtcattg 120 gggatttaaa tttaggagac ttgtttgtac ttaaacttgg cttaataagt gttctttaga 180 gcttgttttt ctttttgtta t 201 <210> 114 <211> 201 <212> DNA <213> Homo sapiens <400> 114 cacacaaaac tgtttctttg gcttgacgaa tacagttaag ccactgctgt ttgttgaaag 60 tgtcattggc ttgtagcgag tgggtctgac tttgggatcc rtttttgaaa ctgactctga 120 agaagttttt aactagaaag gaaaaacaca tgaaaaacaa agtcaatgga cagatccttc 180 ctcaggccaa agagaacaca c 201 <210> 115 <211> 201 <212> DNA <213> Homo sapiens <400> 115 tcctttatag caatgcaaat ggacaccctc cctgtgctgt gtcctgaaat ccctttcaag 60 actggaagtt ggagcaattg cagggctcac ctcatttata yctcttctct tagggtcact 120 gtccttcatt gcctgatgtc cagtgtcttc aaagctatag ctttataggt tttttcatct 180 ttttgttttt atttcagttg c 201 <210> 116 <211> 201 <212> DNA <213> Homo sapiens <400> 116 attcctgtca tattgttgag aacaaattcc ctagtgattc tatgaaataa gatagtattt 60 tatataataa tttggaatcg aatttttctc tgtcatctga mgttacattt cctacttcta 120 ttttatatga aattaatact ctgttttctc acttaattta aatcctgcct gtaaactgtc 180 atgaatgata tgaattaaat a 201 <210> 117 <211> 201 <212> DNA <213> Homo sapiens <400> 117 gaaagtgggt gaacaaaaga cacagggttt tagagacgtg tgtatgtaac tgaagccatt 60 gtatcttgga atacaaggac agttgcacaa aagcagtatg ygatatgtag tcccattcct 120 agatatcatt ggccattttc ctagccagac accaaatagc atgtgataca taaaaataaa 180 ttgatccaat aatagctagg a 201 <210> 118 <211> 201 <212> DNA <213> Homo sapiens <400> 118 tgattgaata aaacacagca gaattagatt tctcaacaaa aatagaacca gaaacacctg 60 tgcacaattg cctagggtgg aataagtgac cttcaggaga rtagggttaa ggtgaagaat 120 tctgaatgcc caaggtggcc tttgggtcag aactggagga atagccttaa tacaaggaga 180 taaccttaca atatttttcc t 201 <210> 119 <211> 201 <212> DNA <213> Homo sapiens <400> 119 atctttttta acataccatt tcaaaacaag gatttgttat gaaaaaattg tctttatccg 60 tcattacttt ttctcatgtt attgtttttt atgcactaaa wagatatgag ttcttgaaat 120 attggtacag ctttctgaat atataaaagt atattaataa aaatagagag ctgagtttag 180 ctttcttttt gtgactttta t 201 <210> 120 <211> 201 <212> DNA <213> Homo sapiens <400> 120 ctttctctcc ctgagatgct ggggtggtca tgagtgcctt ggagaataag ctgaaagccc 60 tagactttgt cttcagagaa aaaatggaca tactcacaca sgtaaaaatt gacattcacc 120 ttcaggccgt ctcctaaaat ctgcctgggt aatagaatag ggtgtctggt aaaatactag 180 cctgggcttg actccagccg g 201 <210> 121 <211> 201 <212> DNA <213> Homo sapiens <400> 121 attagaaagt tttgttgaaa ggacatagat ctaaagatgg ttgagtaggg attacacaaa 60 ttaatgaagg gacaaatgga aatcacattc actcactcga waaacaatta agcacctatt 120 ttgtagcaga gactatagat acaattctgg gttaacaaag aagaatgaga tgtacctgtc 180 atctatttct taacagcttg g 201 <210> 122 <211> 201 <212> DNA <213> Homo sapiens <400> 122 gaagcttgaa aaggagctgg gtgaggcaaa catgcaaatc atgccatgga gattggcaga 60 aaagacgctt gcctccaatt tatggaatgc caagttaatt ygagcccata ggaatgttgt 120 tcccatagat ttagattttt atgaatatat acatatttat gaaagaaaac atttaaagtg 180 tttaattcag taacttatgc a 201 <210> 123 <211> 201 <212> DNA <213> Homo sapiens <400> 123 agaagttaaa tctgtgaaaa aatctttaag tcatcaaata tatacaatta attccacaat 60 ctggaattct cactggcatt tagtcaaaat ggaagttctc ractctcaag aatatattca 120 agaacacaga gtattcagct gtaaatgcaa caattttttc tttgttgatg ggaattgggt 180 gaaatatgat ctttcagatt t 201 <210> 124 <211> 201 <212> DNA <213> Homo sapiens <400> 124 caccacgctg gtcccttcca gaggtgctgt aggtcctctg cctgtaggtc ctctgggcgg 60 actctagttc ctaactgatg gatgatgctg ggccccgctg ytgatgctgc ttaattcata 120 atttggggac tcaagtctct gcaggctcca ctgggccaac ttgcttcctg cagagataca 180 tgttcagact ctactaatta c 201 <110> Korea Research Institute of Bioscience and Biotechnology <120> Multiple SNP markers, microarray and diagnosis method for Sasang constitution <130> 9p-05-06 <160> 124 <170> KopatentIn 1.71 <210> 1 <211> 201 <212> DNA <213> Homo sapiens <400> 1 tggggatcct tacaggccac tcacaatggt aatgagagtc cacatttact gagcactcac 60 tacacaccag ccactcttct caagggcttt ccatgtggaa ytgcaccaaa tccttacaac 120 aaccctctga ggctggggct ggtgctgtat ccattctaca gaggaggaac ctgagacaag 180 gaagggtgag ggcttgccaa g 201 <210> 2 <211> 201 <212> DNA <213> Homo sapiens <400> 2 tggagccaac aaaccttccc tttagcatgg gcctagcgct cccttgccca ctgccagctt 60 tgttactctt agatccttaa tctctgttaa tctgatgact rtaaagcaaa aggttacttt 120 aatttgcatt ttcctggcaa ctggggagag gctgcatctt ttcaggtcat tgtgtgtctt 180 gtttcctctt ctgataattg c 201 <210> 3 <211> 201 <212> DNA <213> Homo sapiens <400> 3 ccaacttcaa attttgaacc tgtttaggga tctgttaatt aaagcagccc ctgcctccca 60 cacatccttc tcctctctgt ttttgttatc tactttcttc ratatggatt agccacttac 120 ttgaattaat ctgtttttca actttcaaaa gttagttaaa tttcccagta ttttggtgtg 180 cctactttgt tttttgacat t 201 <210> 4 <211> 201 <212> DNA <213> Homo sapiens <400> 4 ctggtctacg gtatttttgt tatagcagtc tgaactaacg aagacatatg gtactccata 60 ctggtgagaa aggttcttct cagcaagcct cattcttttt ygctttttga aaacctattt 120 ttttcttttt aaaaaaatcc catggcagca tattaatttt tttttctacc tggcagcaga 180 tcagattctt ttgccatggc t 201 <210> 5 <211> 201 <212> DNA <213> Homo sapiens <400> 5 ctttgcttgc aggaagcagt gcaaactgta ttttggaaca caggttcttt ctgacctggg 60 tccttatctt ctgccattta cctcttggaa gacttacgtt stactgacgc tggactactt 120 gacatttcct atccaagttg tgtctccagg cccttatcta tgctgctccc actgcctgga 180 ataccctttc cctctgccat g 201 <210> 6 <211> 201 <212> DNA <213> Homo sapiens <400> 6 actattgtcc cttcctgaag aaggaagtct agtcttcagg taagaggaag gtatattctt 60 aggcagctgc tgggttggaa ggaaggaaca gtgaagtctg ygttttggaa gggaggaggg 120 agtgacattt ttaagttaca agcctcttct gggagagctg gggacagatc tatttttaga 180 tgtgttccct gacacccagg a 201 <210> 7 <211> 201 <212> DNA <213> Homo sapiens <400> 7 tgcctctgcc aggccccacc tgctccactg cctctgttct gttgcagtga agtgctccgt 60 gtgcaagagc gtctcggaca cctacgaccc ctacttggac rtcgcgctgg agatccgggt 120 acagatctgt cctgcccttc acttttgcag taggagagcg aggccagagg gtgaaacaga 180 acccgcagaa cagtaaaggc a 201 <210> 8 <211> 201 <212> DNA <213> Homo sapiens <400> 8 ggactttatc aaagatggct gactagatgc agctgggaag tgctgtcctc acagagagaa 60 accaaaattt tgactacacc aacataattt gaacagatct ktgatgagaa aacaccaaat 120 gtggatgggg aaaagacaca gttgctgagt cggaagaggg ggaaagctgg gaatcccatg 180 tggagtgccc aaatgctgtg g 201 <210> 9 <211> 201 <212> DNA <213> Homo sapiens <400> 9 actatgctgt ttacaaagca ctttcatatg caggatctca tctgtattca gaggctcact 60 ggtgccctag gcagggatga tgttatcctg gagtaacggc rtaacttagt ctgtgaatga 120 cacaggacac attcttggca actctgtagg acagggcatt tggtccagac aggacactca 180 ccgggctaca aggtctagcc c 201 <210> 10 <211> 201 <212> DNA <213> Homo sapiens <400> 10 ccaatgtctg ctccaatatt ttgtaattga catgtatctg agtctaagag attaaaccaa 60 ctggcacacg acccaacagc atctttggtg attaaaagaa sattggttgt tgcctaaata 120 aaacctgggg ccacgttcgc ccccaggagg acccagtgct aatctcaaat cctgagaacc 180 agtcatttgg gctgggcaaa t 201 <210> 11 <211> 201 <212> DNA <213> Homo sapiens <400> 11 caaattcttc tagagataaa tatttttagt gtcttgaaaa tatattgcca aattttcccc 60 taaaacatgt ataagaatgc tcattttacc atacaatcac ygggcttgaa tatccatttt 120 aagtttaacc agccttaatg attccgttgt actttttttt tttttttttt tgagacgggg 180 cctcactctg tcgcctaggc t 201 <210> 12 <211> 201 <212> DNA <213> Homo sapiens <400> 12 tccaagggga aaaactatct taaaaaataa ttttctatgt attataaaga aagctcgggc 60 ctgttcaacc caacaattct gagttttcaa gtcattctat ragcaggtca accagaaatt 120 gcctgaaccc cctcccatag ccaaaaaact attcacccaa ctggcagaaa gcataaccag 180 cagcttgccc atctcttcat g 201 <210> 13 <211> 201 <212> DNA <213> Homo sapiens <400> 13 agggagaatc tacaccagga aaccataggc tcctgaggtt gaatgcaagt tgcgtgtgtt 60 cctatgtgca aagagaagcc atagctatca ttttctgagg ygtccaagac ccacaaaaag 120 ccaaagactg cactacccga gagactgcag caggaatgag tggattaagc cattcagcat 180 gtccagacat acaaaatcac t 201 <210> 14 <211> 201 <212> DNA <213> Homo sapiens <400> 14 catcgtgagc aatgtattta aggcctccca aaacaaaata atattagcat gacgtatatt 60 tggttaagtg tcataagtat cttaaagcac catccctttc maatctcctt tacagaacat 120 cactaagctg acctctgtat tacaaggcta agaataataa gttttaaaga gtgacaattt 180 tagaattttt cacaatggta t 201 <210> 15 <211> 201 <212> DNA <213> Homo sapiens <400> 15 tgccttttat aagttatgga acattaacat gaaatacata tagaatggaa tttggtagct 60 tgcattacat aaatttattt tggcgagtga agcccatagt yctcaaatcc gattcataaa 120 attaaaacct cttattttct tctggagcct ttaagggctt ttgaaaatca cagttaaaag 180 gtccagattc ttatcgttca t 201 <210> 16 <211> 201 <212> DNA <213> Homo sapiens <400> 16 tttcgaaggg aaaatgattt tatagaaagg gatgggtaac ctttatgata aaattgcttt 60 gctagagcgt gttgcttgtg acagcaccac ctttctgttc ytgacaatgt ttgtcttctt 120 aactaaacaa acgttagctg agttgaatga aattatgtac gaaccagaga agtcgggagg 180 atgtttgagg ctcgagcccc c 201 <210> 17 <211> 201 <212> DNA <213> Homo sapiens <400> 17 cctgtttgta gcccagctac aaacagaaga accaccaagc tgacttgtaa actataacat 60 gtgcttcttc atttaaagct tatttaaagt tgttgaactt ygggttggtt tggttcacag 120 aaatagctaa ccaataaaaa tgaataaaaa attctggtat gttcagaaaa tgaaattcaa 180 agatgaaaat gaacacatta t 201 <210> 18 <211> 201 <212> DNA <213> Homo sapiens <400> 18 gaatatggaa aataaaacca cttttggggt tggggtttcc tcaagccatt cttatttact 60 gagtcggttg cctctggaaa cttttagctc atgtaactaa rcatcgttca ctgccctgtt 120 ctttatgcat ctcagtaagt tccacctgca gaatggtgaa attttgaagt ggaaaggacc 180 ttgatcataa attagttcaa t 201 <210> 19 <211> 201 <212> DNA <213> Homo sapiens <400> 19 tatttaagtc atttgcactt gtgtgtgttt gtaagaactt acgtataaaa tgttcctagt 60 agattttaaa aatgatatta ttttaatatg aaattggcta rtgaagttct agagaattaa 120 tgtttacatt ttgacaacca aattccttat gtactttaca tgtgtttact taaaagtctt 180 acaaaataga atttgccctt c 201 <210> 20 <211> 201 <212> DNA <213> Homo sapiens <400> 20 tgataatgtt ctggcaggtg gcagaaaagc atattgcaga agaggtattt tttctgattt 60 gcacaaaggc atcatattgg atagatgcaa ttgtgagttc yttaactgtt tctttttccc 120 attccttttg cgatacctct ctacctttac tcttctagta tttcctggct atgaaattgg 180 ctaagggcag tggtggcaga a 201 <210> 21 <211> 201 <212> DNA <213> Homo sapiens <400> 21 taactgattt tctacttagc atgctgtttt taaggttcat ctatgttcta gcatgtatca 60 atacttcatt ccttttatgg ctgaataatg tttcattgtc yggctatact acattttatt 120 tatctattta tcagttgata gatatctggg ttgtctccac cttttagcaa ttacaaatag 180 tgctgctata aatatttgtg t 201 <210> 22 <211> 201 <212> DNA <213> Homo sapiens <400> 22 gaaattgatt aaatatggct cttttcctaa gcagatgaat aactctatat tgctcgttct 60 gcatgcctat aaaataatac aatgaacaat gttgacttca kaattgagaa catactccca 120 ttttgctagg tataggcaaa agagaaaaca caagctaaaa cctcaatatc aaggtaatgt 180 ttatagcact atattttcac a 201 <210> 23 <211> 201 <212> DNA <213> Homo sapiens <400> 23 ccttacctgg gagccatcta ctctggaaac catggatacc tacacatctg tgcaaaattg 60 acacagtgcc tcagttattt gggtaaggct gaccagtgaa ytctgataaa ttgctgtaac 120 aatgaccacc catctgtcaa tgtgtcacca agcataggct gtatacactg tgcagactgt 180 aaggatccac tgggctttcg g 201 <210> 24 <211> 201 <212> DNA <213> Homo sapiens <400> 24 tttaaaaaaa actttctgtg aggttcttgg agaagaacct atgaatgagt atgaattccc 60 cttgtgtctg tgacccccag ggtttttaga gactcttgtt ygcttataat aaacctttag 120 caattagtta aaaaatttag cttacttttt cttaccattg tccagtagta tctgtttcag 180 gtaagcaagt gcttgtgact c 201 <210> 25 <211> 201 <212> DNA <213> Homo sapiens <400> 25 gaccttttga catatagggc ctagctgtaa tacatttcaa tgttcagtct ccatcccaag 60 gtgaacatgg gtcatatgtt atatacatat tgtttcaata ygcccgtgtc aggactacct 120 tcatgagtat acatagcact tcctgcaacc tattgaatat gtatgtttag ccagccgggt 180 tggcataaag ctcctacccc a 201 <210> 26 <211> 201 <212> DNA <213> Homo sapiens <400> 26 atagatcaaa atagcctggt ttgttacttc ctcaggtagc tagattatgt ctggattcca 60 gattttgttg tctgaaaagt aagcttctca ttgcttaagt stctcttata ggtttctctc 120 atatgtagcc aagtacaatt catgatgata tagtaaataa aacacatgat gttgtcctca 180 gcaaacctac agttttacaa a 201 <210> 27 <211> 201 <212> DNA <213> Homo sapiens <400> 27 ccgcagcccg gtggctcaga cctgcgaagg aaccaaggca agagggagaa aagccctgcc 60 gcctgatccc acgccgccac tcacagaccc ttcgttgacc sgcagcattg aacaggaaaa 120 aaaaaaaaag atgaaaacac agaaaacccc aaaaacccag acggggagac gatgtgggga 180 agagaacgtg ctgggagcct c 201 <210> 28 <211> 201 <212> DNA <213> Homo sapiens <400> 28 tatgattaca ggaggtacct ggagtagtca aatttataga catagaaagg aggatggtgg 60 ttgccagaat gggtagaatg gggagtggtt atttttcatt yttctgagat gaggtctcgc 120 tctgtcaccc agggtggagt atggtggtgt gatcatagct cactgcaact tcaaattcct 180 ggactcaagc aatcctccca c 201 <210> 29 <211> 201 <212> DNA <213> Homo sapiens <400> 29 gtgtacttca gtgggttttt gtagtggctg gtaatgatct ttccctatca tatttagtgc 60 accttttagg acctcctgta aggcaggtct ggtgataatg mattttctca gcatttgctt 120 gtctgaaaag gatttttatt tctctctcac ttatgaagat tggtttggct ggatatgaaa 180 ttcttggttg aaaattattt t 201 <210> 30 <211> 201 <212> DNA <213> Homo sapiens <400> 30 acctttccct tctgttaaca cggcggtaat ttattacata agagatgtta atcctgggga 60 gaaattctaa atactcaggg aataagtaat ggctgggccg yaaatgatga aaatgtgaat 120 gtgttacata gattctgaat tattcctggc attccctggg gagagagaat agaagtaagt 180 tgcaatcagt tgtgatacct c 201 <210> 31 <211> 201 <212> DNA <213> Homo sapiens <400> 31 ggctgccgtc aaaagtgcat ggacgagtaa agcctggcat caccagggaa tgaaaaaccg 60 cacagtgaat gacctcggcc tggcagtccc acacttaaaa mtcgattgtg aaggcatgct 120 gagaaaggca ccagatgatt tgtgtccaga cctgttcgct ggacggagtg aaaaggtgtg 180 caacacataa agggccggcg g 201 <210> 32 <211> 201 <212> DNA <213> Homo sapiens <400> 32 atgaaatcat tttaggctgc tattggtcat ctataatatt tttaaaatct gccaaagatg 60 tcaccaaaga aggttccatt gtatattatg tgtaacatga rggaattaaa caaataaaat 120 gaataaagtg tttatacatg aaaaaatatc aaaagtgtgc atactggata cctgacttcc 180 atcccaagaa taatttcctt c 201 <210> 33 <211> 201 <212> DNA <213> Homo sapiens <400> 33 aataattagt gttcataaca tttggaattt cagtatgttt aaattcatat tatgagaaga 60 tcaacaggct tattatgttt gcataaatat tagtataggc ygcttttatt atagaataaa 120 gaagaataaa cattcttttg tcttttcaaa atacagctat gcacatacac atgaacacaa 180 aactatcatt tacaaattat t 201 <210> 34 <211> 201 <212> DNA <213> Homo sapiens <400> 34 agttcctgcc ctccagttgc tcacagtcta gcaagggatg gaggagacta attaagaaac 60 cttttattac agcacagctg actgcacgaa ccaaaggaga mgcatgagcc agagagacaa 120 ggaaggcttt caaaggaagg gatggtcaag ctgggtttcc aaggatgact aggagctggc 180 caggcagcaa agggcattcc a 201 <210> 35 <211> 201 <212> DNA <213> Homo sapiens <400> 35 acctcctgct gtgtggcccc gttcctaaca ggccacggac cagtaacagt ccaaggccca 60 ggggttggga atcctgcctt aaggcgcaga gcagttacat yatggcactg aagtttatac 120 atcagtttct tgaaagtttc attatcatgt gtctttcccc aggactgacc agctctcagc 180 acaacttttt aagaaaatga a 201 <210> 36 <211> 201 <212> DNA <213> Homo sapiens <400> 36 aatggctaaa tccatgtcaa aatgtgcaga ataatataat cttatactgt ttcacctatc 60 aaattagcaa ataattttaa aagttctatt cctcatagcc rgtgtgcata tgctgagaga 120 agtccttttt tttcctgtgg gaagcttaat tgataggaaa ataattaatt gaaaaataat 180 ttgacagtat gtaccaattt t 201 <210> 37 <211> 201 <212> DNA <213> Homo sapiens <400> 37 ttccaatttc tagacttttc atgaaatatg ggaagggtgt aaccagaagg actactacat 60 ggtaccttta ggccttgact gtcagtaccc ctccatcagc rtgagtcttg ggcagagctg 120 ggcatcagtg aacagacaca gtgaccaggt acctggcctt cctcacccct tgctgccctc 180 tggccctcaa agccttgagc c 201 <210> 38 <211> 201 <212> DNA <213> Homo sapiens <400> 38 tggaacacag gttctttctg acctgggtcc ttatcttctg ccatttacct cttggaagac 60 ttacgttgta ctgacgctgg actacttgac atttcctatc saagttgtgt ctccaggccc 120 ttatctatgc tgctcccact gcctggaata ccctttccct ctgccatgcc caccaggtga 180 atcacagctt atcctttaag a 201 <210> 39 <211> 201 <212> DNA <213> Homo sapiens <400> 39 ctccacttac tggctattct ttggtttctc tcctctcctt gagccttcct atgccctcag 60 atacaacagt attgaaattt gatcaattag taatcctata rtggtctcta agtgttcaac 120 tgaaaggaaa agttgcgcat ctttctttct ttaccgagac agggtctcgc tctgttgccc 180 aggctagaat gcagtggcgc a 201 <210> 40 <211> 201 <212> DNA <213> Homo sapiens <400> 40 tattttgcat gtaagaagga caaaaatttg ggggtgctgg gcagaatgtt aatgagtgaa 60 tatgttctag aaaaagcgca ttgaaggaga gaaaaatgtg ygagaaagag accaatccat 120 ggtgaaaagt cagtggttta cactccagag aagaactaat cagctctgtt tttatatagc 180 ataagtttaa catgctggga a 201 <210> 41 <211> 201 <212> DNA <213> Homo sapiens <400> 41 caccgcacct ggccccctag caggttcttg atagttgctg acaatggagc tagctgggga 60 ttctttcctc cgatggtcat tatgcattat agacaaggtt yctgtgttct cattatgccc 120 ccaaggaaca tgcttcagca aacgtgaaaa atgccagagc catacatttt tttttttttt 180 tttttgagac agggtctccc t 201 <210> 42 <211> 201 <212> DNA <213> Homo sapiens <400> 42 ggtcacaatt gtgcctctgt gcaggcatgc ttgcgcccct agccttctag tgtttatcct 60 tgctgatctt ttgatttctc tcacagaacc ttggatacct ygtttcccat ttcctggtga 120 ggtcaccacc ctctccggtg gtggcgctgg gccctgatct ttgctgtttc tccaccccat 180 gtgttctgtt tcgcttccat t 201 <210> 43 <211> 201 <212> DNA <213> Homo sapiens <400> 43 agacggggtt tctccatgtt ggtccggctt gtctcaaact cccgacctca ggtgatccac 60 ctgccttggc ctcccaataa catccctact ttaggctaca ycatatataa tgagtttagt 120 tggttaatgg ctacccaaat tcaagtagta agcaaagtac ctttatgcct tgagaggcat 180 gaaaacagca gcctccaggc t 201 <210> 44 <211> 201 <212> DNA <213> Homo sapiens <400> 44 gttcccaagc aggaagctgg ggcgtgatta aatggatgcc ggacaaccaa aaaagcaaaa 60 gcccgcttca cagccacatc cagtgtctaa atccacatca yctaaaagta cctggaagat 120 cataggcttc ctcgtcaggt cctccaaggc cacttccatg atcctgcttc taggactggg 180 accccacccc cttcacacgg c 201 <210> 45 <211> 201 <212> DNA <213> Homo sapiens <400> 45 tagaatggga gacagatttt ccctgagtgg ttcccagctt gaaagggcct aagatatttt 60 cctttcacaa gaggtatgcc cgtaatacct tgaagaactt ygtgtaacaa ctaaataaat 120 aaatggtaac aaattagcac tcaataaatg tcagctatta gcttttccaa ataatcctaa 180 aatgtgcaac ctcttgttta c 201 <210> 46 <211> 201 <212> DNA <213> Homo sapiens <400> 46 tggtcctcat tctgcacctt gctgttctgt tctatgtaac atccaggctg ggaggggagg 60 gggccggccc tcctcctctg tcccaggctc tgcagtgggc racttggttc cgtccttacc 120 tcctcagctg ggcatgtgat cttggtgctc tgagccttgt tctctgtgct aagtatatgg 180 ggttcattgg aaaaactgac a 201 <210> 47 <211> 201 <212> DNA <213> Homo sapiens <400> 47 aaggatgaga tcaggtatgg tcagcatccc tcacctccca aatcctcttc caagtcattc 60 ctcttgcacc cttgtgtgaa aacccttcct cctttgagag rctatcaatc tggctctatc 120 acagtgtcag tcaaaattcc cttggatgta aacaacagaa actggctggc tgatgtagcc 180 tgaaaatgaa tgtattcaaa a 201 <210> 48 <211> 201 <212> DNA <213> Homo sapiens <400> 48 caggcccatt ttgcagaggg gaagactgag gtgcagtgat gcaaaatgtg tggtggaggg 60 ctgggcctgg aatctgggag ttctggttcc gggtgaccgt mcactagaaa gggaaaggtg 120 gcagaaccat atatatgagc ctgttacttg ttcaaggact tggtcagggg cctcacagaa 180 cttggaaaag agcaacggac t 201 <210> 49 <211> 201 <212> DNA <213> Homo sapiens <400> 49 catgtgttcc ttatagttca tccatccaaa aaaattgcag ttcctcaatg ttacactctc 60 ttggtctgtt ctcttagtgt aatcttcccc atacacattc yttgaccaaa attaaccttt 120 aatacttagc tcactttggg aggccaaggc aggtggatca cttgaggtca ggagttagag 180 accagcctgg ccaatatgat g 201 <210> 50 <211> 201 <212> DNA <213> Homo sapiens <400> 50 ccactcccca agccaccagg tggccctgcc cacacctgga ttcatttaac cccatgagac 60 cgtgtcggac tcctgccctc cggaattgcc agctaataca kttgtgttgt tcaaaccact 120 gaagttcatg gtcagatgtt atgacagcag aaatagcctg atacactgtg agaaagtgga 180 gagcacacga cgcctcggga a 201 <210> 51 <211> 201 <212> DNA <213> Homo sapiens <400> 51 gggagctagt taggcaatta gtacagtcgt tgagaaaaca ggtaatggta gcttaaacta 60 acaggaggat aaaggagaag agaagtacat gggttttcaa yacatctaag aggtaagcta 120 gcagggtttg gctatcaatt gggcatgaaa agtaagggag gggaatgtat cataagagta 180 acgtctcggt tttagagtag a 201 <210> 52 <211> 201 <212> DNA <213> Homo sapiens <400> 52 caagtgaatc actaatgaca tttgttggtt tattggttga aaagtacttg ctgtagataa 60 actatccacc aggccatgtg ctcttcttca cctcagaacc rtgccttagt ttatcactag 120 ctgcctcctt ctctttcttt atatcctagc ttcaatggca gtctttcctc atcactttct 180 ctaattaaac cacctattct a 201 <210> 53 <211> 201 <212> DNA <213> Homo sapiens <400> 53 acaagtctct aaatgaggta cgtaagttat tactccagac atcagggagt attttgttta 60 tgaaacatct ccaatttatc actagctggt tatcattatt ytcctcataa atctatagat 120 gctggtttta ttttctataa gccatcctta gccaaggaca tcccattatg acctttccct 180 agataaggac tccattccta g 201 <210> 54 <211> 201 <212> DNA <213> Homo sapiens <400> 54 tataattttt tagaaatagc tgtgacatga aatatggcct tgacagagaa tgaagaacat 60 atcaagaaca acaaatgacc aacatgaatt gtctctgata ygctatttca tttacctgtt 120 tatgaaatgg aatatttcta gtgctcttta tcatcaaatg caaatggaat atgtgaggag 180 gcctggcagt tccaccagga t 201 <210> 55 <211> 201 <212> DNA <213> Homo sapiens <400> 55 agaatcttga agatttacct gttcccatag gtactgcagc attattcata atcattaaga 60 tatggaaaca acttagatgt ccattgacag atgaacgaat raagacaatg tgatatctat 120 ctatctatct atctatctat ctatctatct atctatcatc tatctatcta tatcatctat 180 tatctatcta tctatcatct a 201 <210> 56 <211> 201 <212> DNA <213> Homo sapiens <400> 56 aggtctttac aatttggcat gtttttgcag tggctggtac cagttgttcc tttccatgtt 60 tagtgcttcc ttcaggagct cttgtaaggc aggccttgtc rtgaaaaata tctctcagca 120 ttttcttgtc tgtgaaggat tttatttctc cttcacttat gaagcttagt ttgtctggat 180 atgaatttct gtgttgaaaa t 201 <210> 57 <211> 201 <212> DNA <213> Homo sapiens <400> 57 catgagaccg tgtcggactc ctgccctccg gaattgccag ctaatacagt tgtgttgttc 60 aaaccactga agttcatggt cagatgttat gacagcagaa rtagcctgat acactgtgag 120 aaagtggaga gcacacgacg cctcgggaaa acacctcctt ggctgggttt tgctaaagca 180 aaaatagaaa tccaatttag t 201 <210> 58 <211> 201 <212> DNA <213> Homo sapiens <400> 58 ttcctggagg tgaactctta ctcatgctat agaactcttc ccccaattcc cccgctctgt 60 gagttatccc atcataagac agacgcaatc tcaaatttct stattcattc tccaacagtt 120 atgacaacgg ccagcattca ttgagcatgt actaattgcc agacactatt ctaagctctt 180 tacacttttc tttctctctc t 201 <210> 59 <211> 201 <212> DNA <213> Homo sapiens <400> 59 accaaggttt ccaaagctgt tgaataaatg aaaggtaaat aaaaatgcat tgaaccccaa 60 aaaagctgct gaagggaatt ttcataatgg aagggaagta ytttttgctg aagggaatct 120 ttacaaaagg aagcattttt gatgcttgtt tttaagagat atacgtatat atacattaat 180 aaatacacat atttacgtta a 201 <210> 60 <211> 201 <212> DNA <213> Homo sapiens <400> 60 tgctcttctc gaggagtatc tttgtggtgt tctctgtatt tcctgaatct gaatattggc 60 ctgccttgct aggttgataa aattctcctg gatgatatct kgcagagcgt tttccaactt 120 gtttccattc ttcccatcac tttcagctac accaatcaaa catagatttg gtcttttcac 180 atagtcccat atttattgga g 201 <210> 61 <211> 201 <212> DNA <213> Homo sapiens <400> 61 taaaaaatag gagaaaatct ttttgacctt gtattaggct aaagattatt agatatgatg 60 ccaaaagaat aatctataaa agaacaaatg gataaattgg wcttcataca cataaaaaac 120 cttcagctcc ccaaatgata ctgttaaaaa aaatgaaaag acaactacag gctggaagaa 180 aatacttata aagtgcatgt c 201 <210> 62 <211> 201 <212> DNA <213> Homo sapiens <400> 62 tttttttgtg ttcttgtttt ttggagcatt aaaagacagc acttcctttc tactatatga 60 caacccttca aatcaatgaa agagctgtta tgattgtcct rctatgatcc taagttaaac 120 ccatgagttt tcctcatctg ctcaacatgt ggtattgcct tcagaatctt cactagtctg 180 gtcactctac tgttgataga a 201 <210> 63 <211> 201 <212> DNA <213> Homo sapiens <400> 63 cccatgagtt ttcctcatct gctcaacatg tggtattgcc ttcagaatct tcactagtct 60 ggtcactcta ctgttgatag aatcaacctg ttcgtgattg ycctaaaatg tgattaccca 120 gggagggatc acttagtttg ggctgcagtg ggactatgaa tcctgtgttg aaattacaaa 180 ctacttttat tggcctggcc t 201 <210> 64 <211> 201 <212> DNA <213> Homo sapiens <400> 64 ccctcacctg ccgtgcctga cacccgccag caacacacac ttgggaccag tcctgctgcc 60 ctgtcacccg gcatggctga ccctgaccgg ggccttttcc ragctgctgt agctcatctc 120 agcccaatgc cactgggaga cattgcagca catctctcac cttcgactgt ggaatatttg 180 aggacaggcc tgtgactcac c 201 <210> 65 <211> 201 <212> DNA <213> Homo sapiens <400> 65 ttcatcatac ccacccagat ttttagccct gtgtgtgcat acctgttgga aacaaagacc 60 acatttccca gctcccatgg agctagatgt tgcaatgtga mtaagttttg ctcaacgaag 120 catgagcaga ggtactgggt gacttctagg aagtgtcctt taagggtggg gcacaacctt 180 ctgcccttcc tccttcttat a 201 <210> 66 <211> 201 <212> DNA <213> Homo sapiens <400> 66 taatatgagc caagtttttg ttccctgtgt caggtactga cacagtggca ctcagtgctc 60 tactacagtt ggcttatttt taatcatttc aattatcctc rggtagaaca tcatccttga 120 ctgagagaac aggaaactga ggacaacaga cgtttgaaaa tgtgttaatg tttcacagat 180 aatggcagag gacccctgga t 201 <210> 67 <211> 201 <212> DNA <213> Homo sapiens <400> 67 ggacataata ttagacatag tcatagaaat ccttaataaa atattagcag atagaattaa 60 tcaatatatg aaaagtgtat ggtgtataca tgatcaaggg rgttttattc caccgatgct 120 tgatatttga gaatcaatgt acaatcatga catagtaaac ataacccacc acagtaacag 180 gctaaaggaa ggtaatcata t 201 <210> 68 <211> 201 <212> DNA <213> Homo sapiens <400> 68 gcctcaaagc tcctgcaccc ccagcacttg ggctgaccaa agagaacagc agggactttt 60 cttgtgtgtc acccaaggaa gaaggaagtg acaaacaatg rccaaagata ggggtggaga 120 ccttaaatgc ccacaggggc caacaggtat tgtaaccaag tggcaaggcc agctgaagac 180 actagggagg ctgaagacag g 201 <210> 69 <211> 201 <212> DNA <213> Homo sapiens <400> 69 agttattcat tctgtataac tgaaattttg tactctttga ccaacatctc ctcatctctc 60 cctccccaca gtccctggca atcaccattc tactttctga ycttatgagt ttgacttttt 120 tttagattcc tcatgtaact gagatcacgt ggtctttacc ttcagtgtgg agaaaaggga 180 acctttttac atggttggtg g 201 <210> 70 <211> 201 <212> DNA <213> Homo sapiens <400> 70 tttataaatt atccagtctc agggaaattc tttatagcag tgtgagaatg gactaatata 60 aggggcaaag agaatcattc ctggacagct ctgtagactg ytgcaagaac tattccagtt 120 gaagacaaat gtgtgactct gccctgctgg tgagctttgt tttctctcct atattcatcc 180 aatgaatctg acgtctaggt t 201 <210> 71 <211> 201 <212> DNA <213> Homo sapiens <400> 71 tgggctttcc tccaagtgtg aaaccctgga tgcgttctga aatccccaag gatgctgaga 60 gccacagacg tgtagacgga aagaaatcaa accattcgcg ytgctgatgg tgggaggaag 120 tgcgctgcag cccgcacctg cctcccctga tgccaacagc aggaccggca ccctcgttct 180 ctgcagtcac actccccatg t 201 <210> 72 <211> 201 <212> DNA <213> Homo sapiens <400> 72 tggaccagaa aaagaaaatg aggtgacaga caaatgtatc atctattttc agtgaagagt 60 tgctccctcc aggaaagcca tttgtgatta tttaattgcc rtgaaatttt cctcaggttt 120 aataactagc atgcagggaa aatcatttat tacatgaata cttgcaataa tcaaaatata 180 tttagaagat tttaataatt t 201 <210> 73 <211> 201 <212> DNA <213> Homo sapiens <400> 73 ataatgtttc catggaaaag tctgcttcca ggcttattga ggctgcattg catgttattt 60 ctttcttttc tcttgtgctt taggatcctt tctttatcct ygacctttgg aagttagtga 120 ctgttagttg ccttgaggta gtcttctttg ggttaaatct gcttggtgtt ctataacctt 180 cttggagtta actgttaaca t 201 <210> 74 <211> 201 <212> DNA <213> Homo sapiens <400> 74 ccccgagtcc ctactattac accaggtctc ccctgcctag agaagtgagc cttacagctg 60 aatgcacatt tcatagaaac caagaggtta ctcttcattg ycgaagtgaa gcattagtct 120 tgtaaaatta aaaaaaaaaa aaacaggcca tctttgagtg aataatgaga tacttgcctt 180 aatttgattc ttaattataa t 201 <210> 75 <211> 201 <212> DNA <213> Homo sapiens <400> 75 acatttgggt tttgtttcca tatggtggtt attgtgaata acgctgcaat gaacatgtga 60 gtgcagatat atctacaagt actactttca tttcctatgg ktgtatatcc agaagaggga 120 ttgctgaccc acatggtagt tctattttta atttttcaat gagcctcatg ctctgtcccc 180 taatggctgt tccaatttac a 201 <210> 76 <211> 201 <212> DNA <213> Homo sapiens <400> 76 catttaagtg gaagaggata atgtgtcatt gatcttgagg tagttggtaa aagtgagaga 60 gaaaaataca ccgtaggaaa accaaacaaa acaaaactgg rccatttagc ctggcaggga 120 cagaaataag gagaccctta agagaggagt ttgaaatcac agtaaaaagt gcaagtgatg 180 tgatacaata gaaaacacgt t 201 <210> 77 <211> 201 <212> DNA <213> Homo sapiens <400> 77 gggagagcta gccttaaaat gtaaccgaga ttaagaaagg cagaggaaaa acaaaagaaa 60 aaaatataaa caaaagaaag aaatgacaac ctcattgtaa yggtaaatca agtcaaaatg 120 gaagccagag gcaccagtgg gcttttaaaa ttacgtaagc taataatttc cctttattgt 180 taagccagtt tgagttggct t 201 <210> 78 <211> 201 <212> DNA <213> Homo sapiens <400> 78 ccaaggacag agcactgaga ctgtaaagga ctaggagaca ctgatcacta tggggagggg 60 atatccctgc atgcaggaca acaggaccca ggctagatac rggtaaatgc agatttcctc 120 tgctactgac actgtttaga taccgtgaga cattctgagt atgaagttga agctagtagc 180 aaactactca aagattaaat a 201 <210> 79 <211> 201 <212> DNA <213> Homo sapiens <400> 79 aaaaacctat gagaatattt tgcagtgaga gtttagtttc atttttgttt actttgcttt 60 tgcatcaata atatcttcaa gagaagaaac attagacaga kttttagtag ttaggtcaac 120 tcctatcagt ggttttcata cttttctttt tttccggatt cctttgtgaa agtaaatttt 180 ctgatgttga attgttttca g 201 <210> 80 <211> 201 <212> DNA <213> Homo sapiens <400> 80 gcagtccaca gtgtttacag agtgggacta tatacagtca cccttctctc acccgtcctc 60 cctgctctga gacacacccc tgtggcgagc accgcagaaa ygggaagcca ctacttaaga 120 tcggaagtta agagagctcc ctccgaagag aaaattttta tactaaaatc tataatttaa 180 ttcaagagaa tgcttttatt t 201 <210> 81 <211> 201 <212> DNA <213> Homo sapiens <400> 81 aagccaccat ccctggccaa ccgtacatac ttttttaaat gtatcagagg aaagaaacag 60 gacacaggtt ggggatagaa tctagctttg tctgaatgta mcttgttttg gaaccatgta 120 aatattttac atacttagta aaatacattt aaattttgaa aatgtaccct ctaaaaactg 180 aaagcagagc aaatgtattg a 201 <210> 82 <211> 201 <212> DNA <213> Homo sapiens <400> 82 ccactttccc tttgcttttg aggaacattt cagaaactat gttcaacaaa tactactgaa 60 tttgtattga attggccaag acaataattg aaaccagaaa kaaagttttt cattgggaaa 120 tggtttctac taacaaattt agtatgtcca cattaaaaaa ggtgagagat tatatcacct 180 tctctagatt gctacttttc t 201 <210> 83 <211> 201 <212> DNA <213> Homo sapiens <400> 83 gggtggactt tggggagtct gcatgctctc cagctagtgt tgcctgtggg gagcaggttt 60 gcaaggtttg gggagcattt tggcagcttt ggagagaaca ytgaagaagg atggaccctt 120 aaggcccaag ggagtgattg gtagagcctc tggagcagga ctgggcctga gatgtgggct 180 ctggaacttg atgctagaga g 201 <210> 84 <211> 201 <212> DNA <213> Homo sapiens <400> 84 ccacgagtgt ccgcaggtgc acagaaacat gggcagtggg atgtttccat gggtcaccta 60 attccagcca aggtggacaa accttcctga acagaatggg ygttgtcagt gtggagaagt 120 atccacaggc tatggccgca gaagctgctg gatggctgag aggcgtctcc aggaaataaa 180 tggggtgcct gttagatagc a 201 <210> 85 <211> 201 <212> DNA <213> Homo sapiens <400> 85 cacatcaaat catctatcaa ttctttctcc atctctcaag cccaactctc ccttgccctc 60 tccagaccat gtgtgcatat cacctgggtc gtcttcattc yctaaatcac ctacgccttt 120 tccttggctt tctcaatttc ctgaggcaca ttcttcaaga gcttgctaag taaagaccca 180 tggagaatac acttttagcc a 201 <210> 86 <211> 201 <212> DNA <213> Homo sapiens <400> 86 agtggcaaag tcactttgca gagcagtgtg cagaaaatta tctgcatctg aaaaagaaca 60 tattgggagt tttattcaga ttgagctgga tacataaatc rtcttggact gaattaacat 120 cttaacaata gtggattttc taattcttga ataccatata tttgttatat gttttaaata 180 tttatgtttg aaaagttttg t 201 <210> 87 <211> 201 <212> DNA <213> Homo sapiens <400> 87 cctttatata gaatgcttat aatagtattg cttatattgt gaaaaaagtt aactagcaga 60 ttgaataaat aaatccatgt gacagggaat tggcagccac raacatattg gtggtagatt 120 aatacataat atataataac atttaattat tttgtatatg gcttactaaa atatataagt 180 ataattaatg acataatgat a 201 <210> 88 <211> 201 <212> DNA <213> Homo sapiens <400> 88 ttttggaata aattggcagg gctcaggaat gtggtagaat gaagaagata agagaattct 60 tgcactctct ggaaaagctt tcagcacaag gagaatggag wttagctttc cctatactgg 120 atgaccctca gtaataatta aggtatttga atgttctgtc cttaacacct gagcttgata 180 aagaacctac tttcagttct t 201 <210> 89 <211> 201 <212> DNA <213> Homo sapiens <400> 89 actgtgaggc accacaccag ccctgggctg cttatgtttc tattactacc tgagaaaaat 60 aaaactctat ctgatttgag tcactattgt tttggggtct yggttatagc agctgacctg 120 tatttaaatt aatacacatg gacacagatg aagcctagtg gaggcttcta agatacaaga 180 tgggggcttg tgtttggaca t 201 <210> 90 <211> 201 <212> DNA <213> Homo sapiens <400> 90 gccaagtaga agctaaagtt ttctcatctc ctcctcttct ctttctctat cgctctttca 60 tgatgcaagt gacaactaat taaataaaac tatctgtgaa wtacatgtgc attgagacct 120 cccagagaca aagatgcaac cttctgccag ccccaaatcc aatctctgct gttccctgtg 180 cccaggggaa cggacccaat g 201 <210> 91 <211> 201 <212> DNA <213> Homo sapiens <400> 91 aaaactctca gaaatgctgg ttaacatata atggacatcc ttttacatat aaatttctag 60 gggccaaaaa aagaagaggg aactgaaaac ctaagtggca rttgtatcca ccctttaatt 120 tcacttgggg cagagaagat aaggtctgtg ccaagtaaag acttggaact gagagcttcc 180 tccccaccaa ccccattgca t 201 <210> 92 <211> 201 <212> DNA <213> Homo sapiens <400> 92 gtggaagagg aactctggaa gcaaacaggc tttagcaaaa gtgatgtaac caaaatggaa 60 tcagatacag attggggaat ctcatcaaca tttacctgta ygcttaaccc agttgtgaca 120 gttagaaaca tgatagttgt ggtgtctggg ggagggtggc atagtggagg ggttgagggt 180 gtggcctctg gagccagggt t 201 <210> 93 <211> 201 <212> DNA <213> Homo sapiens <400> 93 tttgaatgtt ctgtccttaa cacctgagct tgataaagaa cctactttca gttctttgat 60 ctgtgtgtaa cccagcaatg cctctcatcc ctagtgttca mccgagttta tagtctttgc 120 cagagaaaag aaagcatcat tagagaaaca ggccaccagt ttcttctcct gacacttgga 180 tacttcacaa tgtgagttaa a 201 <210> 94 <211> 201 <212> DNA <213> Homo sapiens <400> 94 aaaccaactc ccctggtgct ggaatggttt gtattgtacc atagcatatt atgtggctta 60 tttctaaaat agttagaatt taaatgaatc atgaaaatgc rattaaaaca cactatggtt 120 acaaagattt ttttaaatct aaaacttgga tcttatattt aattgatgat ttgtcattct 180 gtaattttta tattccttgg c 201 <210> 95 <211> 201 <212> DNA <213> Homo sapiens <400> 95 ctcttcccac ttagatttct ctttcattgc ctcatttggc ttcttttcct ctcttggtgt 60 ctctgtgcta acccacttta tttcacttta cactttcttc rgcagcagtg ccatccactc 120 ccatcccttt cttctcttgc cttctctgtt ccttttctat caatgtgctc agcattcctc 180 ctgctcccac taaattggcc a 201 <210> 96 <211> 201 <212> DNA <213> Homo sapiens <400> 96 agtggaagac aagtgttgag acaagccaaa ggttgcgaca aaggcgtaga aaccatccac 60 cttgtcaaat gggctctcat ccttttcaaa gtggagccat kccatgtaga gcagacactg 120 caagcttgat gggaatgagg catatctggc tcaaaagcat gtttatttgt gtgtttttaa 180 aagtgtaaat attgaaccaa c 201 <210> 97 <211> 201 <212> DNA <213> Homo sapiens <400> 97 agggactttt tcactctggg ttagatcatg aaagttaaag tattgggttt gaactgcata 60 aaaaaacaaa caaaatgtgt gtgtcatgat tctagattgt sctaacctat ccagcaagtt 120 caaaactgtg aactattggc taacagacaa gcatgagagt atggctggat aaatgctaga 180 tttatatcat ttgagagaaa a 201 <210> 98 <211> 201 <212> DNA <213> Homo sapiens <400> 98 atattggtac agctttctga atatataaaa gtatattaat aaaaatagag agctgagttt 60 agctttcttt ttgtgacttt tatatttaat aactccaatg watttgatga aacacaaata 120 aatcagctca gaagaattta actgtaatac gtatgctaat attgtttgca ttcaatctgt 180 aagggaatca gaaaccgaag t 201 <210> 99 <211> 201 <212> DNA <213> Homo sapiens <400> 99 agtttggaaa tattacctcc atttttcaga atagtttgag taggattggt atttcttctt 60 ttttatatgt ttggtattac ttcttttata tgtttatcaa wgaagccatc aagttctggg 120 cttttattta ccttgagact tttattagat ctttggtctc attacttcac atgagcctgt 180 tcaggttttg gatttcctca t 201 <210> 100 <211> 201 <212> DNA <213> Homo sapiens <400> 100 ttatatgtta cgttttctac tatttaaatt tcaggcactt cagtggactt caattcatca 60 actcttctac aagagcacgc ttactttctg acactgacct saatcttctt ttcctttgtt 120 agagaataat taaagcctca tatgtagaag cagggctgta aagtcacact gctaagagta 180 ccaatcttgt gactgcagct g 201 <210> 101 <211> 201 <212> DNA <213> Homo sapiens <400> 101 ccagataggg ccttgtagtc cttttaaaaa ctctggcagt tattccagtt gaaaaggtga 60 gcctctgcgg ggttctgatt aaagggttca ctctagttat ygtgtcaaaa tagaaaagaa 120 gcaaggaaga gtaaaagaag gcagaccaat gaggaggtga ttggagcagt ccaggcaaga 180 gtgtttgagg gcttggagca g 201 <210> 102 <211> 201 <212> DNA <213> Homo sapiens <400> 102 aagaacagtt gttttcttta tcttcccttt gagtcctgtt cgaattaaaa tgtatgtttt 60 acaagcattc aaaaaggtaa tggattgttt cacaagtaaa ktcctaagtg ttcagctatt 120 tcagctcttc tttgccattt ggggcttctt acttgttagg tgatttctcc ggccttctat 180 caagcatgat gtgtgtcttc c 201 <210> 103 <211> 201 <212> DNA <213> Homo sapiens <400> 103 ttctctacta agacaactac aatcatatat ttgtgtggaa ttacatatct acataagtgg 60 aaatttattt aatgtcctta catattgtct tgttcattag ytgtctttga aagtcatttt 120 aaaaatcttt gtattacctg cctcaaaagg ttgctaggaa gattggataa aataataaat 180 ataaagcagt gaaatcaatg c 201 <210> 104 <211> 201 <212> DNA <213> Homo sapiens <400> 104 tcatctcttt cgtgtttcta cttaacatta aaaatatgga atacagctat aacaactgtt 60 ttaacatcct tgttggctaa ttctaacatt tctgtcaggt staagtcagt ttggattggt 120 ttttatgttt ttcttctatg ggttgtgttt tcctgctttg catgtcttgt agtctttcat 180 tagatggcag gcactgtgaa t 201 <210> 105 <211> 201 <212> DNA <213> Homo sapiens <400> 105 ggtcacagaa ataacaaggg acttctgtag atcactgcaa gaactttagc atttaccata 60 aatgagattt ttaaaaccac tgaaagcttt tgcaagtaca rgaaaggcat gacctgattt 120 gcattttaaa aaatcatctg gcttctgtct tgaaaataaa atgtgagata aatcggggag 180 accggttagg aggttattgc a 201 <210> 106 <211> 201 <212> DNA <213> Homo sapiens <400> 106 aactcctcac ctcaagtgat ccaccttcct cagcctccca aagtgctggg attacaggcg 60 tgagccactg cactcagcct gtcatctccc atttgcttgt rtaaacgcct gaggctgtgg 120 taggatcctg ccctaaggat agcaattagg gcttggctgc aaggaaggcc cacaggactc 180 aaaatgacaa tgtgtacaca c 201 <210> 107 <211> 201 <212> DNA <213> Homo sapiens <400> 107 aagttctagt tccagtggaa aatttggccc cttggaacta tcagcaacca gcacttcagt 60 catagacctg gctatgttta ccttgtgctt gctttgagtc ytgttgaagt cagttgggaa 120 cacatcatag gtccatcagg attctatgct cgggagacat ggcaagccct atgtgagaag 180 ggtggcaagg aatggcatac a 201 <210> 108 <211> 201 <212> DNA <213> Homo sapiens <400> 108 ggaaatgatt ttgttctttt ttatggctgc atagtattcc atggcatata tgttacgtac 60 cgcagttttt aatccaatcc accaccaatg ggcatcagaa ktgatttaag tctttgctac 120 tgtgaaaaac atatgagtac atgtgtcttt ttgatagcat gatttatttt tctttgggta 180 gatatccagt aatgggattg c 201 <210> 109 <211> 200 <212> DNA <213> Homo sapiens <400> 109 aagcactggt tgacttttgg tgggcaacct gaaagagagc tgtgaatgac atctctcctc 60 cctgctccta actagagagt gtgtctcaga gaactgtgcc rtttaagagc cggaaggcac 120 tctcaaagcc acctggttca atatttccca aagaggagca ttttctgttc atacaatagg 180 atattatttt agcttatgca 200 <210> 110 <211> 201 <212> DNA <213> Homo sapiens <400> 110 cctcctaaat caaccttaga cccacattag ctttcacctg gtgtgactgc tttagttgcc 60 tgttgtctgt gctgctgtcg ctttctccct actaaagcca ycctctgttt tactacctga 120 ttaacctcct ccaagcacac acctaagcac accaccctcc catttacaac cagcaggctc 180 aaaacctttc agtggctccc a 201 <210> 111 <211> 201 <212> DNA <213> Homo sapiens <400> 111 tgctggaggc agagggtgcc aggatgcagc tgtgagccag agaatgccaa ggattttcag 60 ccaccccaaa agctaggaag aggcaaggaa gatttctacc ktgagtttct gatagagtat 120 ggcaatgctc ttgatttggg acttctagcc ttgagaattg tgaaataata catgtatatg 180 ctttaagccc ctccaatttg t 201 <210> 112 <211> 201 <212> DNA <213> Homo sapiens <400> 112 caacacgacc tccctcacat ggctgggggt tgatgctggc tgcaagctgg gagttcagct 60 gggcctatca ggaagggacc tgaactcttc tctatgttga yctctccacg tggctacttg 120 ggcttcctca cagcatggtg actgagttct aagaagaagc actccaagag gcaaaggctg 180 gagctgtgtc atttccgcca t 201 <210> 113 <211> 201 <212> DNA <213> Homo sapiens <400> 113 cttaaataat tctgtgatcc tggctcccga taagaggaaa ttgtctttcc aaaaggcata 60 atagcctcct agggatttgc tttcctttga acaatgaaga rggaggaaaa ggtgtcattg 120 gggatttaaa tttaggagac ttgtttgtac ttaaacttgg cttaataagt gttctttaga 180 gcttgttttt ctttttgtta t 201 <210> 114 <211> 201 <212> DNA <213> Homo sapiens <400> 114 cacacaaaac tgtttctttg gcttgacgaa tacagttaag ccactgctgt ttgttgaaag 60 tgtcattggc ttgtagcgag tgggtctgac tttgggatcc rtttttgaaa ctgactctga 120 agaagttttt aactagaaag gaaaaacaca tgaaaaacaa agtcaatgga cagatccttc 180 ctcaggccaa agagaacaca c 201 <210> 115 <211> 201 <212> DNA <213> Homo sapiens <400> 115 tcctttatag caatgcaaat ggacaccctc cctgtgctgt gtcctgaaat ccctttcaag 60 actggaagtt ggagcaattg cagggctcac ctcatttata yctcttctct tagggtcact 120 gtccttcatt gcctgatgtc cagtgtcttc aaagctatag ctttataggt tttttcatct 180 ttttgttttt atttcagttg c 201 <210> 116 <211> 201 <212> DNA <213> Homo sapiens <400> 116 attcctgtca tattgttgag aacaaattcc ctagtgattc tatgaaataa gatagtattt 60 tatataataa tttggaatcg aatttttctc tgtcatctga mgttacattt cctacttcta 120 ttttatatga aattaatact ctgttttctc acttaattta aatcctgcct gtaaactgtc 180 atgaatgata tgaattaaat a 201 <210> 117 <211> 201 <212> DNA <213> Homo sapiens <400> 117 gaaagtgggt gaacaaaaga cacagggttt tagagacgtg tgtatgtaac tgaagccatt 60 gtatcttgga atacaaggac agttgcacaa aagcagtatg ygatatgtag tcccattcct 120 agatatcatt ggccattttc ctagccagac accaaatagc atgtgataca taaaaataaa 180 ttgatccaat aatagctagg a 201 <210> 118 <211> 201 <212> DNA <213> Homo sapiens <400> 118 tgattgaata aaacacagca gaattagatt tctcaacaaa aatagaacca gaaacacctg 60 tgcacaattg cctagggtgg aataagtgac cttcaggaga rtagggttaa ggtgaagaat 120 tctgaatgcc caaggtggcc tttgggtcag aactggagga atagccttaa tacaaggaga 180 taaccttaca atatttttcc t 201 <210> 119 <211> 201 <212> DNA <213> Homo sapiens <400> 119 atctttttta acataccatt tcaaaacaag gatttgttat gaaaaaattg tctttatccg 60 tcattacttt ttctcatgtt attgtttttt atgcactaaa wagatatgag ttcttgaaat 120 attggtacag ctttctgaat atataaaagt atattaataa aaatagagag ctgagtttag 180 ctttcttttt gtgactttta t 201 <210> 120 <211> 201 <212> DNA <213> Homo sapiens <400> 120 ctttctctcc ctgagatgct ggggtggtca tgagtgcctt ggagaataag ctgaaagccc 60 tagactttgt cttcagagaa aaaatggaca tactcacaca sgtaaaaatt gacattcacc 120 ttcaggccgt ctcctaaaat ctgcctgggt aatagaatag ggtgtctggt aaaatactag 180 cctgggcttg actccagccg g 201 <210> 121 <211> 201 <212> DNA <213> Homo sapiens <400> 121 attagaaagt tttgttgaaa ggacatagat ctaaagatgg ttgagtaggg attacacaaa 60 ttaatgaagg gacaaatgga aatcacattc actcactcga waaacaatta agcacctatt 120 ttgtagcaga gactatagat acaattctgg gttaacaaag aagaatgaga tgtacctgtc 180 atctatttct taacagcttg g 201 <210> 122 <211> 201 <212> DNA <213> Homo sapiens <400> 122 gaagcttgaa aaggagctgg gtgaggcaaa catgcaaatc atgccatgga gattggcaga 60 aaagacgctt gcctccaatt tatggaatgc caagttaatt ygagcccata ggaatgttgt 120 tcccatagat ttagattttt atgaatatat acatatttat gaaagaaaac atttaaagtg 180 tttaattcag taacttatgc a 201 <210> 123 <211> 201 <212> DNA <213> Homo sapiens <400> 123 agaagttaaa tctgtgaaaa aatctttaag tcatcaaata tatacaatta attccacaat 60 ctggaattct cactggcatt tagtcaaaat ggaagttctc ractctcaag aatatattca 120 agaacacaga gtattcagct gtaaatgcaa caattttttc tttgttgatg ggaattgggt 180 gaaatatgat ctttcagatt t 201 <210> 124 <211> 201 <212> DNA <213> Homo sapiens <400> 124 caccacgctg gtcccttcca gaggtgctgt aggtcctctg cctgtaggtc ctctgggcgg 60 actctagttc ctaactgatg gatgatgctg ggccccgctg ytgatgctgc ttaattcata 120 atttggggac tcaagtctct gcaggctcca ctgggccaac ttgcttcctg cagagataca 180 tgttcagact ctactaatta c 201
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KR20180082801A (en) * | 2017-01-11 | 2018-07-19 | 인제대학교 산학협력단 | Composition for diagnosing sasang constitution and diagnosis method using the same |
KR20190059882A (en) * | 2019-05-23 | 2019-05-31 | 인제대학교 산학협력단 | Composition for diagnosing Taeeumin and diagnosis method using the same |
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KR102193659B1 (en) * | 2019-06-21 | 2020-12-22 | 한국한의학연구원 | SNP markers for diagnosing Soyangin of sasang constitution and use thereof |
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KR102193657B1 (en) * | 2019-06-21 | 2020-12-22 | 한국한의학연구원 | SNP markers for diagnosing Taeeumin of sasang constitution and use thereof |
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KR20180082801A (en) * | 2017-01-11 | 2018-07-19 | 인제대학교 산학협력단 | Composition for diagnosing sasang constitution and diagnosis method using the same |
KR20190059882A (en) * | 2019-05-23 | 2019-05-31 | 인제대학교 산학협력단 | Composition for diagnosing Taeeumin and diagnosis method using the same |
KR20190060961A (en) * | 2019-05-23 | 2019-06-04 | 인제대학교 산학협력단 | Composition for diagnosing Soyangin and diagnosis method using the same |
KR20190060962A (en) * | 2019-05-23 | 2019-06-04 | 인제대학교 산학협력단 | Composition for diagnosing Soeumin and diagnosis method using the same |
KR102193659B1 (en) * | 2019-06-21 | 2020-12-22 | 한국한의학연구원 | SNP markers for diagnosing Soyangin of sasang constitution and use thereof |
KR102193658B1 (en) * | 2019-06-21 | 2020-12-22 | 한국한의학연구원 | SNP markers for diagnosing Soeumin of sasang constitution and use thereof |
KR102193657B1 (en) * | 2019-06-21 | 2020-12-22 | 한국한의학연구원 | SNP markers for diagnosing Taeeumin of sasang constitution and use thereof |
KR20210132277A (en) * | 2020-04-24 | 2021-11-04 | 한국 한의학 연구원 | SNP markers for diagnosing Cold Hands/Feet Syndrome and use thereof |
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