KR20120043793A - Snp for diagnosing hip dysplasia in dog and uses thereof - Google Patents
Snp for diagnosing hip dysplasia in dog and uses thereof Download PDFInfo
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Abstract
Description
본 발명은 개 고관절 이형성증 조기 진단용 SNP 및 이의 용도에 관한 것으로서, 더욱 상세하게는 서열번호 1 내지 25로 이루어진 폴리뉴클레오티드에 있어서 각 SNP(single nucleotide polymorphism) 위치 염기를 포함하는 10개 이상의 연속 염기로 구성되는 폴리뉴클레오티드로부터 선택되는 하나 이상의 폴리뉴클레오티드 또는 이의 상보적 폴리뉴클레오티드로 이루어지는 개 고관절 이형성증 조기 진단용 SNP(single nucleotide polymorphism), 상기 SNP의 폴리뉴클레오티드, 이에 의해 코딩되는 폴리펩티드 또는 이의 cDNA를 포함하는 개 고관절 이형성증 조기 진단용 마이크로어레이, 상기 마이크로어레이를 포함하는 개 고관절 이형성증 조기 진단용 키트 및 상기 SNP 위치 염기를 이용하여 개 고관절 이형성증의 조기 진단 방법에 관한 것이다.The present invention relates to an SNP for early diagnosis of canine hip dysplasia and its use. More specifically, the present invention relates to a SNP (single nucleotide polymorphism) position base in a polynucleotide consisting of SEQ ID NOs: 1 to 25. Canine hip dysplasia comprising SNP (single nucleotide polymorphism) for early diagnosis of canine hip dysplasia consisting of one or more polynucleotides selected from polynucleotides or complementary polynucleotides thereof. An early diagnosis microarray, a canine hip dysplasia early diagnosis kit including the microarray, and a method for early diagnosis of canine hip dysplasia using the SNP position base.
모든 생물의 게놈은 진화의 과정에서 자손의 서열에 변이체를 생기게 하는 자발적 돌연변이를 겪으며 다형(polymorphism)이 발생한다(Gusella, Ann. Rev. Biochem. 55, 831-854, 1986). 상기 다형에는 RFLP (restriction fragment length polymorphism), STR (short tandem repeats) 및 SNP (single nucleotide polymorphism) 등이 알려져 있다. 상기 SNP는 인간의 경우 약 1,000 bp 마다 1회의 빈도로 발생하는 것으로 알려져 있다. 이들 SNP가 질병과 같은 표현형에 영향을 미치는 경우, 상기 SNP를 포함하는 폴리뉴클레오티드는 이러한 질병을 진단하는 데에 사용될 수 있다. 상기 SNP에 특이적으로 결합하는 모노클로날 항체 또한, 질병의 진단에 사용될 수 있다.The genomes of all organisms undergo spontaneous mutations that produce variants in the progeny sequence during evolution and polymorphisms occur (Gusella, Ann. Rev. Biochem. 55, 831-854, 1986). Restriction fragment length polymorphism (RFLP), short tandem repeats (STR), and single nucleotide polymorphism (SNP) are known as the polymorph. The SNP is known to occur once in about 1,000 bp in humans. If these SNPs affect a phenotype such as a disease, the polynucleotides containing the SNPs can be used to diagnose this disease. Monoclonal antibodies that specifically bind to the SNPs can also be used for the diagnosis of diseases.
전 세계적으로 개의 품종은 약 400여 종이 있으며, 이는 인간의 과도한 육종의 결과라 할 수 있다. 이에 따라 개는 근친교배율이 높아져 각종 유전질환에 노출되어 있다. 개의 유전질환으로 고관절 이형성증, 비만, 백내장, 퇴행성 망막위축증, 알레르기, 간질 및 신장질환 등이 있으며, 유전 질환에 대한 DNA 시험은 주요 위험 변이체를 제거하는데 중요한 정보를 제공해준다. 현재 DNA 시험이 활용되고 있는 개의 유전 질환으로는 왜소발육증(독일 세펴트), 퇴행성 망막위축증(마스티프) 및 악성 발열(전 품종) 등이 있으며, 분자생물학적 기법을 통해 지속적으로 개발되고 있다.There are about 400 breeds of dogs worldwide, which is the result of excessive breeding of humans. As a result, dogs have high inbreeding rates and are exposed to various genetic diseases. Genetic disorders in dogs include hip dysplasia, obesity, cataracts, degenerative retinal atrophy, allergies, epilepsy and kidney disease. DNA tests for genetic diseases provide important information to eliminate key risk variants. Genetic disorders in dogs that are currently being used for DNA testing include dwarfism (Germany), degenerative retinal atrophy (mastiff), and malignant fever (all breeds), and are being developed continuously through molecular biological techniques.
2004년에 개 유전체 초안이 해독되어 질병, 체형 및 행동에 대한 유전체 정보의 활용도가 높아졌다. 개가 가지고 있는 고유의 DNA 정보는 특정 표현 형질을 대표할 수 있으면서 유전적 정보에 의한 선발에 활용될 수 있다. 분자 마커는 유전자 마커로서 선발의 정확도를 높이고 질병과 같은 질적 형질을 조기에 진단할 수 있는 매우 유용한 기술이다. 현재, 개의 DNA 시험을 서비스하고 있는 일부 회사는 퇴행성 망막위축증, 왜소증 및 간질과 같은 유전 질환 관련 유전자의 SNP (single nucleotide polymorphism)를 상업화된 분자표지들로 이용하여 반려견 산업에 활용하고 있다. In 2004, draft dog genomes were deciphered, increasing the availability of genomic information on disease, body type, and behavior. The unique DNA information of a dog can be used for selection by genetic information while being able to represent specific expression traits. Molecular markers are genetic markers that are very useful for improving selection accuracy and for early diagnosis of qualitative traits such as diseases. Currently, some companies serving dog DNA testing are using the commercially available molecular markers (SNPs) in genes related to genetic disorders such as degenerative retinopathy, dwarfism and epilepsy in the dog industry.
개는 반려동물로서 인간의 정서를 풍부하게 하는 현대사회의 중요한 동물자원이다. 국내 반려동물시장은 약 1조 원으로 추정되고 있으며 반려동물의 질병진단키트의 생산규모는 2007년 기준 7억 원 수준으로 외국시장에 비하면 낮은 수준이며 국내 개의 DNA 시험 서비스는 전무한 수준이다. 그러나, 반려동물에 대한 국민적 관심과 시장의 꾸준한 확대를 고려한다면 지속적인 성장이 예상된다. Dogs are important animal resources in modern society that enrich human emotions as pets. The domestic pet market is estimated at about 1 trillion won, and the production scale of the disease diagnosis kit for pets is about 700 million won in 2007, which is lower than that of foreign markets, and there are no domestic DNA test services. However, considering the national interest in pets and the steady expansion of the market, continued growth is expected.
본 발명의 목적은 유전질환이 없는 우수한 개를 선발하는데 정확성을 높이고, 유전 질환과 같은 위험요소를 제거하면서 유전능력 개량을 극대화할 수 있는 유전자 마커를 개발하는 것이다. An object of the present invention is to develop a genetic marker that can maximize the improvement of genetic ability while improving the accuracy in selecting excellent dogs without genetic diseases and eliminating risk factors such as genetic diseases.
한국등록특허 제10-0754398호에는 심혈관 질환 진단용 다중 SNP가 개시되어 있으며, 한국등록특허 제10-0933065호에는 아스피린 민감성 천식 진단을 위한 SNP 유전자 세트가 개시되어 있다. Korean Patent No. 10-0754398 discloses multiple SNPs for diagnosing cardiovascular disease, and Korean Patent No. 10-0933065 discloses a set of SNP genes for diagnosing aspirin-sensitive asthma.
본 발명은 상기와 같은 요구에 의해 도출된 것으로서, 개의 고관절 이형성증은 여러 유전요인의 결과로 알려져 있기 때문에 78개의 염색체 전체의 유전자 변이를 분석하여 고관절 이형성을 조기진단할 수 있는 유전자 마커를 개발하기 위하여, 개 22K SNP 칩을 이용하여 단일염기다형(SNP)을 발굴하고 개의 고관절 이형성증과 유의적인 단일염기다형을 발굴하여 조기에 진단, 예측할 수 있는 유전자 마커를 개발함으로써 본 발명을 완성하게 되었다. The present invention is derived from the above-mentioned needs. Since hip dysplasia of dogs is known to be a result of several genetic factors, it is necessary to analyze genetic variations of all 78 chromosomes to develop genetic markers for early diagnosis of hip dysplasia. The present invention was completed by discovering a single nucleotide polymorphism (SNP) using a dog 22K SNP chip, and developing a genetic marker that can detect and predict early hip dysplasia and a significant single nucleotide polymorphism.
상기 과제를 해결하기 위해, 본 발명은 서열번호 1 내지 25로 이루어진 폴리뉴클레오티드에 있어서 각 SNP(single nucleotide polymorphism) 위치 염기를 포함하는 10개 이상의 연속 염기로 구성되는 폴리뉴클레오티드로부터 선택되는 하나 이상의 폴리뉴클레오티드 또는 이의 상보적 폴리뉴클레오티드로 이루어지는 개 고관절 이형성증 조기 진단용 SNP(single nucleotide polymorphism)를 제공한다. In order to solve the above problems, the present invention is one or more polynucleotides selected from polynucleotides consisting of 10 or more consecutive bases each containing a single nucleotide polymorphism (SNP) position base in the polynucleotide consisting of SEQ ID NO: 1 to 25 Or it provides a single nucleotide polymorphism (SNP) for early diagnosis of canine hip dysplasia consisting of a complementary polynucleotide thereof.
또한, 본 발명은 상기 SNP의 폴리뉴클레오티드, 이에 의해 코딩되는 폴리펩티드 또는 이의 cDNA를 포함하는 개 고관절 이형성증 조기 진단용 마이크로어레이를 제공한다. The present invention also provides a microarray for early diagnosis of canine hip dysplasia comprising a polynucleotide of the SNP, a polypeptide encoded therein or a cDNA thereof.
또한, 본 발명은 상기 마이크로어레이를 포함하는 개 고관절 이형성증 조기 진단용 키트를 제공한다. The present invention also provides a kit for early diagnosis of hip dysplasia of the dog comprising the microarray.
또한, 본 발명은 상기 SNP 위치 염기를 이용하여 개 고관절 이형성증의 조기 진단 방법을 제공한다. The present invention also provides a method for early diagnosis of canine hip dysplasia using the SNP position base.
본 발명의 개 고관절 이형성증 조기 진단용 SNP를 이용하면, 유전적으로 발생하는 진행성 질환인 고관절 이형성증의 위험성을 갖는 개에 대한 특별한 관리를 준비할 수 있고, 번식을 위한 교배를 할 때 중요한 유전적 정보를 예측하여 고관절 이형성증이 없는 우수한 개를 선발하는데 유용할 것으로 사료된다. By using the SNP for early diagnosis of canine hip dysplasia of the present invention, it is possible to prepare special care for dogs at risk of hip dysplasia, which is a genetically advanced disease, and to predict important genetic information when breeding for breeding. Therefore, it may be useful to select excellent dogs without hip dysplasia.
도 1은 개 4번, 38번 및 X 염색체상의 고관절 이형성과 연관성이 있는 SNP의 위치를 나타낸 것이다. 1 shows the location of SNPs associated with hip dysplasia on
본 발명의 목적을 달성하기 위하여, 본 발명은 서열번호 1 내지 25로 이루어진 폴리뉴클레오티드에 있어서 각 SNP(single nucleotide polymorphism) 위치(서열번호 1의 경우 123번째, 서열번호 2의 경우 120번째, 서열번호 3의 경우 119번째, 서열번호 4의 경우 122번째, 서열번호 5의 경우 119번째, 서열번호 6의 경우 122번째, 서열번호 7의 경우 87번째, 서열번호 8의 경우 124번째, 서열번호 9의 경우 121번째, 서열번호 10의 경우 119번째, 서열번호 11의 경우 120번째, 서열번호 12의 경우 190번째, 서열번호 13의 경우 122번째, 서열번호 14의 경우 120번째, 서열번호 15의 경우 145번째, 서열번호 16의 경우 131번째, 서열번호 17의 경우 118번째, 서열번호 18의 경우 181번째, 서열번호 19의 경우 120번째, 서열번호 20의 경우 120번째, 서열번호 21의 경우 108번째, 서열번호 22의 경우 147번째, 서열번호 23의 경우 119번째, 서열번호 24의 경우 120번째 및 서열번호 25의 경우 122번째) 염기를 포함하는 10개 이상의 연속 염기로 구성되는 폴리뉴클레오티드로부터 선택되는 하나 이상의 폴리뉴클레오티드 또는 이의 상보적 폴리뉴클레오티드로 이루어지는 개 고관절 이형성증 조기 진단용 SNP(single nucleotide polymorphism)를 제공한다. In order to achieve the object of the present invention, the present invention is a polynucleotide consisting of SEQ ID NO: 1 to 25 each SNP (single nucleotide polymorphism) position (123 for the SEQ ID NO: 1, 120 for the SEQ ID NO: 2, SEQ ID NO: 2) 119th for 3, 122th for SEQ ID NO. 4, 119th for SEQ ID NO. 5, 122th for SEQ ID NO. 6, 87th for SEQ ID NO. 7, 124th for SEQ ID NO. 8, SEQ ID NO. In case 121, in case of SEQ ID NO: 10, in case of SEQ ID NO: 10, in case of SEQ ID NO: 10, in case of SEQ ID NO: 10 The 131th time for SEQ ID NO: 16, the 118th time for SEQ ID NO: 17, the 181th time for SEQ ID NO: 18, the 120th time for SEQ ID NO: 19, the 120th time for SEQ ID NO: 20, the 108th time for SEQ ID NO: 21, 147th SEQ ID NO: 22, sequence One or more polynucleotides or complementary polynucleotides thereof selected from the group consisting of ten or more consecutive bases comprising a base 119 for No. 23, 120 for SEQ ID No. 24 and 122 for No. 25) It provides SNP (single nucleotide polymorphism) for early diagnosis of canine hip dysplasia.
상기 서열번호 1 내지 25는 상기 각각의 SNP (단일염기다형, single nucleotide polymorphism) 부위의 염기서열을 포함하는 폴리뉴클레오티드이다. 상기 서열번호 1 내지 25는 다형성 부위를 포함하는 다형성 서열이다. 다형성 서열(polymorphic sequence)이란 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 25 are polynucleotides containing the nucleotide sequence of each of the SNP (single nucleotide polymorphism) sites. SEQ ID NOs: 1 to 25 are polymorphic sequences including polymorphic sites. 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.
본 발명에 따른 개 고관절 이형성증 조기 진단용 SNP를 구성하는 각 단일 SNP의 폴리뉴클레오티드는 바람직하게는 10개 이상의 연속 염기이며, 더욱 바람직하게는 10 내지 100개의 연속 염기이다.The polynucleotide of each single SNP constituting the SNP for early diagnosis of canine hip dysplasia according to the present invention is preferably 10 or more consecutive bases, more preferably 10 to 100 consecutive bases.
본 발명은 또한, 상기 SNP의 폴리뉴클레오티드, 이에 의해 코딩되는 폴리펩티드 또는 이의 cDNA를 포함하는 개 고관절 이형성증 조기 진단용 마이크로어레이를 제공한다. 바람직하게는, 상기 폴리뉴클레오티드는 아미노-실란, 폴리-L-라이신 또는 알데히드의 활성기가 코팅된 기판에 고정될 수 있으나, 이에 제한되지는 않는다. 바람직하게는, 상기 기판은 실리콘 웨이퍼, 유리, 석영, 금속 또는 플라스틱일 수 있으나, 이에 제한되지는 않는다. 상기 폴리뉴클레오티드를 기판에 고정화시키는 방법으로는 피에조일렉트릭(piezoelectric) 방식을 이용한 마이크로피펫팅(micropipetting) 법, 핀(pin) 형태의 스폿터(spotter)를 이용한 방법 등을 사용할 수 있다. The present invention also provides a microarray for early diagnosis of canine hip dysplasia comprising a polynucleotide of the SNP, a polypeptide encoded by the same or a cDNA thereof. Preferably, the polynucleotide may be immobilized on a substrate coated with an active group of amino-silane, poly-L-lysine or aldehyde, but is not limited thereto. Preferably, the substrate may be, but is not limited to, a silicon wafer, glass, quartz, metal or plastic. As a method of immobilizing the polynucleotide on a substrate, a micropipetting method using a piezoelectric method, a method using a pin-shaped spotter, or the like can be used.
본 발명에 따른 마이크로어레이는 본 발명에 따른 폴리뉴클레오티드 또는 그의 상보적 폴리뉴클레오티드, 그에 의해 코딩되는 폴리펩티드 또는 그의 cDNA를 이용하여 본 분야의 당업자에게 알려져 있는 통상적인 방법에 의해 제조될 수 있다.Microarrays according to the invention can be prepared by conventional methods known to those skilled in the art using the polynucleotides or their complementary polynucleotides according to the invention, the polypeptides encoded by them or the cDNAs thereof.
본 발명은 또한, 상기 마이크로어레이를 포함하는 개 고관절 이형성증 조기 진단용 키트를 제공한다. The present invention also provides a kit for early diagnosis of canine hip dysplasia comprising the microarray.
본 발명에 따른 키트는 본 발명의 마이크로어레이 이외에 피검체로부터 해당 SNP를 포함하는 DNA를 분리 및 증폭하는데 사용되는 프라이머 세트를 추가로 포함할 수 있으나, 이에 제한되지는 않는다. 상기 적절한 프라이머 세트는 본 발명의 서열을 참조하여 당업자는 용이하게 설계할 수 있을 것이다. The kit according to the present invention may further include, but is not limited to, a primer set used to separate and amplify DNA including the SNP from the subject in addition to the microarray of the present invention. Such suitable primer sets will be readily apparent to those skilled in the art with reference to the sequences of the present invention.
본 발명은 또한, 피검체로부터 핵산 시료를 분리하는 단계 및The present invention also provides a step of separating a nucleic acid sample from a subject and
서열번호 1 내지 25 중에서 선택되는 하나 이상의 폴리뉴클레오티드의 각 SNP 위치 염기인 다형성 부위의 유전자형을 결정하는 단계를 포함하는 개 고관절 이형성증의 조기 진단 방법을 제공한다. 바람직하게는, 상기 피검체는 개이다. Provided is a method for early diagnosis of canine hip dysplasia comprising determining the genotype of a polymorphic site that is each SNP position base of at least one polynucleotide selected from SEQ ID NOs: 1-25. Preferably, the subject is a dog.
본 발명의 방법에 있어서, 피검체로부터 DNA를 분리하는 방법은 당업계에 알려진 통상적인 방법을 통하여 이루어질 수 있다. 예를 들면, 조직 또는 세포로부터 DNA를 직접적으로 정제하거나 PCR과 같은 증폭 방법을 사용하여 특정한 영역을 특이적으로 증폭하고 이를 분리함으로써 이루어질 수 있다. 본 발명에 있어서, DNA란 DNA 뿐만 아니라 mRNA로부터 합성되는 cDNA도 포함한다. 피검체로부터 핵산을 얻는 단계는 예를 들면, 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)), 자가유지 서열 복제 (Guatelli 등, Proc. Natl. Acad. Sci. USA 87, 1874(1990)) 및 핵산에 근거한 서열 증폭 (NASBA)이 사용될 수 있으나, 이에 제한되지는 않는다. In the method of the present invention, the method of separating DNA from a subject may be performed through 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. In the present invention, DNA includes not only DNA but also cDNA synthesized from mRNA. Obtaining nucleic acids from a subject may include, for example, PCR amplification, ligase chain reaction (LCR) (Wu and Wallace, Genomics 4, 560 (1989), Landegren et al., Science 241, 1077 (1988)), transcription amplification. transcription amplification (Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989)), self-sustaining sequence replication (Guatelli et al., Proc. Natl. Acad. Sci. USA 87, 1874 (1990)), and Nucleic acid based sequence amplification (NASBA) may be used, but is not limited thereto.
분리된 DNA의 염기서열의 결정은 당업계에 알려진 다양한 방법에 의하여 이루어질 수 있다. 예를 들면, 디데옥시 법에 의한 직접적인 핵산의 뉴클레오티드 서열의 결정을 통하여 이루어지거나, SNP 부위의 서열을 포함하는 프로브 또는 그에 상보적인 프로브를 상기 DNA와 혼성화시키고 그로부터 얻어지는 혼성화 정도를 측정함으로써 다형성 부위의 뉴클레오티드 서열을 결정하는 방법 등이 이용될 수 있으나, 이에 제한되지는 않는다. 상기 혼성화의 정도는 예를 들면, 검출가능한 표지를 표적 DNA에 표지하여, 혼성화된 표적 DNA 만을 특이적으로 검출함으로써 이루어질 수 있으며, 그외 전기적 신호 검출방법 등이 사용될 수 있으나, 이에 제한되지는 않는다. 본 발명에 따른 개 고관절 이형성증의 조기 진단 방법은 바람직하게는, 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.
Determination of the nucleotide sequence of the isolated DNA can be made by various methods known in the art. For example, by determining the nucleotide sequence of a nucleic acid directly by the dideoxy method, or by hybridizing the probe comprising the sequence of the SNP site or a probe thereof to the DNA and measuring the degree of hybridization obtained therefrom. A method of determining the nucleotide sequence may be used, but is not limited thereto. The degree of hybridization may be achieved by, for example, labeling a detectable label on a target DNA to specifically detect only the hybridized target DNA, and other electrical signal detection methods may be used, but is not limited thereto. The method for early diagnosis of canine hip dysplasia according to the present invention preferably hybridizes a nucleic acid sample isolated from the subject with a polynucleotide comprising a SNP according to the present invention or a complementary polynucleotide thereof, or a polynucleotide hybridizing thereto. And then detecting the hybridization result.
이하, 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명의 내용이 하기 실시예에 한정되는 것은 아니다.
Hereinafter, the present invention will be described in detail by way of examples. However, the following examples are merely to illustrate the invention, but the content of the present invention is not limited to the following examples.
실시예Example 1: One: DNADNA 시료의 준비 및 개 고관절 이형성증 진단용 Sample Preparation and Diagnosis of Hip Dysplasia SNPSNP 의 선별Screening
고관절 엑스레이 진단 결과를 가지고 있는 고관절 이형성증 위험군 24두 및 정상군 24두로 구성되어있는 레브라도 래트리버 48두의 혈액으로부터 Wizard Genomic DNA Purification Kit(Promega, Madison, WI, USA)를 이용하여 DNA를 추출하였으며, 전체 22,362개의 SNP 정보로 구성되어있는 Canine SNP20 Beadchip (Illumina, San Diego, CA, USA)을 이용하여 SNP 유전자형 분석을 실시하였다.DNA was extracted from the blood of 24 patients with hip dysplasia with 24 hips and 24 normal patients with Labrador retriever, which was diagnosed with hip X-ray, using the Wizard Genomic DNA Purification Kit (Promega, Madison, WI, USA). SNP genotyping was performed using Canine SNP20 Beadchip (Illumina, San Diego, CA, USA), which consists of 22,362 SNP information.
유전자형 분석 후 얻어진 모든 SNP의 자료들은 하디-바인베르그 평형(Hardy-Weinberg equilibrium, HWE)과 마이너 대립유전자 빈도(minor allele frequency, MAF)에 대하여 R/SNPassoc 패키지의 카이-제곱(chi-square) 검정을 실시하여, 일정 조건에 맞지 않는 결과는 배제하였다(HWE; P<0.001, MAF; <1%). 고관절 표현형 관련 양적형질 유전자좌위(QTL) 검출을 위하여, 고관절 표현형과 SNP 마커 사이의 연관성을 검정하는데 SNP 마커 회귀분석(R-통계 패키지, R-Development Core Team)을 이용하였고, 고관절 표현형에 대한 각 SNP 마커들의 상가적 유전효과(additive effect)를 하기 식과 같이 분석하였다.All SNP data obtained after genotyping were chi-squared test of the R / SNPassoc package for Hardy-Weinberg equilibrium (HWE) and minor allele frequency (MAF). The results that did not meet certain conditions were excluded (HWE; P <0.001, MAF; <1%). For the detection of hip phenotype-related quantitative trait loci (QTL), we used SNP marker regression (R-Development Core Team) to test the association between hip phenotype and SNP markers. The additive effect of SNP markers was analyzed as follows.
y = μ + Sexi + SNPj + eij y = μ + Sex i + SNP j + e ij
y : 고관절 표현형y: hip phenotype
μ : 전체 평균 μ: overall mean
Sexi : 유전자형 효과(i: 암컷, 수컷 및 거세한 수컷)Sex i : Genotype effects (i: female, male and castrated male)
SNPj : 유전자형 효과(j: AA, AB 및 BB)SNP j : genotype effect (j: AA, AB and BB)
eij: 임의오차, N~(0, σ2 e)
e ij : random error, N ~ (0, σ 2 e )
유전체전단 연관분석(genome wide association test)과 같은 다중분석(multiple testing)의 문제점인 임의 발생 오류로 인한 오류 검정(false positive)을 위하여 10,000번의 순열검정(permutation test)을 수행하여 0.1% 수준으로 게놈-와이즈 P-값(genome-wise P-value)을 계산하였다 (도 1 및 표 5).To perform false positives due to randomly generated errors, such as problems in multiple testing, such as genome wide association tests, 10,000 permutation tests were performed to achieve a genome of 0.1%. Genome-wise P-values were calculated (FIG. 1 and Table 5).
표 1 내지 3에서 보는 바와 같이 개 유전체상에 존재하는 총 22,362개의 SNPs 중 개의 고관절 이형성증에 유의성을 가지는 SNP를 4번, 38번 및 X 염색체에서 각각 11개, 4개 및 10개씩 총 25개를 발굴하였으며(genome-wise P<0.001), 이러한 유전자형은 개의 고관절 이형성증의 발생 확률을 예측하는데 활용이 가능하여 선발을 위한 유전자 마커로서 효과가 있을 것으로 판단된다.As shown in Tables 1 to 3, out of a total of 22,362 SNPs on the dog genome, 25 SNPs having significant significance for hip dysplasia in 11, 4, and 10
상기 표 1 내지 표 3에 기재된 각 SNP 위치의 염기 중에서, 정상군과 위험군의 염기를 정리하면 하기 표 4와 같다.Of the bases of the SNP positions shown in Tables 1 to 3 above, the bases of the normal group and the risk group are summarized in Table 4 below.
<110> REPUBLIC OF KOREA(MANAGEMENT : RURAL DEVELOPMENT ADMINISTRATION) <120> SNP for diagnosing hip dysplasia in dog and uses thereof <130> PN10191 <160> 25 <170> KopatentIn 1.71 <210> 1 <211> 212 <212> DNA <213> Canis familiaris <400> 1 aaagatccct gtagtccagg gtcactgcaa ctgcaacaga caggcttggg acagacatct 60 gatctgacta cagtcctcac ccactaacaa aatcctctca gggattttgg agcacaggaa 120 gagtgctcca cagtcctgga aaatgagcaa agagtatcta gtctgaccta actacaagcc 180 tcaggtggct ctgattagct tcttaacaaa ac 212 <210> 2 <211> 267 <212> DNA <213> Canis familiaris <400> 2 tttagtggct ctgaacaacc taccatggct ttcgaagaaa atcagctgtg gtcccaagga 60 catttgaaac ttgggcaaag taccaagaaa aggcttatga gggaggcatt gttttggggc 120 gtcttatagc ttggaatcat tatctgcgaa tgaaagttag aagaaagatt tcagcttatt 180 taaagaactt tccattagtc aaaaccatct atagatgaaa caaacacttt tttataaaag 240 aatgaatttc tcattcttta gggcatt 267 <210> 3 <211> 235 <212> DNA <213> Canis familiaris <400> 3 gcagaagttt ctgtgtaagc gccaatccca gttcctgttt atcaccctgc cctagcttat 60 tcgttgttcc ccttacttgc agccgcttta cggtgtaata cgtgtctggc tgcctgtccg 120 tgcagccacc tgaatgtctc tttttggaga aagacagggg tagaagctct gtagcaactg 180 aactctttaa agatttgtat ttatttgaaa gagacagaga gagagagggg cgggg 235 <210> 4 <211> 211 <212> DNA <213> Canis familiaris <400> 4 aggccaggaa tggaagccag tgggtggtga gcatatggga aacagagggc ccacattctc 60 agaagagtga gggagctggg gtgggagtga cagttcaggg tgctgccacg ggaaacagtg 120 gggccatgat gggattctgc tggcccgttg ggagagggtc acctgggtta attaaaaggg 180 tgtccgagtc ctgggaagct tcctccctcc c 211 <210> 5 <211> 257 <212> DNA <213> Canis familiaris <400> 5 ttgttagggg ttccaggtac tcctaggaga aactgccaac tctatgttga gatgaaacta 60 gcacaaccct ggcagggaga tgcagggtgc caaccaaccc ctccacagta tagtttaaca 120 gagaaagctg tggctccagg aaaggaaagg ggtgacccct taccacctat tgtgctgtag 180 ggccctagcc cttatctgct ctcttccagg agcatctgct agaacaaaca gaaactcctc 240 tccccgtatc ctcctgt 257 <210> 6 <211> 262 <212> DNA <213> Canis familiaris <400> 6 gaaagttcag gcttttgtgg gaaagaaacc agatcaacaa catggacttt agggaggtga 60 gaaaataacc actctgggta gtaatatccc ctttggacaa actagactga gagaagccca 120 gggaagtgtt agaatagttt tcagccttga ctggatcaga atcacttgtg gatttttcta 180 aatattttat tcattcatct ctctcacaca cacacaggca gagacataag cagagggaga 240 agcaggctcc ccatggaact tg 262 <210> 7 <211> 211 <212> DNA <213> Canis familiaris <400> 7 cccttatccc catcccatcc agccacatcc aaatgatttt aatatattgt ttaggttaaa 60 ccatccagtt aaaggctaat gcagatctgg gaaggatcag gaaacaagag aaagtgaagg 120 agtgccaagg aaagagttgg tggaagtctg gaggggaaat tagttataaa tgtcaagttg 180 gaagtctaga ggagataaaa aggcagagtg t 211 <210> 8 <211> 216 <212> DNA <213> Canis familiaris <400> 8 gatcagttct catctccttc tttaggtatc taggagatct tgggatgcca atcaggtgtt 60 tgtatctgac tcaacctttc tatgctttac tccccagtat gtgaaatcgt tttcataagg 120 agaggaactt tctgtgggcc acataaacaa agaaacccag aaacagggtt cagcctggag 180 aggagagatt atgattgggg tatcaggact cagggg 216 <210> 9 <211> 211 <212> DNA <213> Canis familiaris <400> 9 ttggtctacc agcagatgac agcggacagg agcccctagg gctggggttg gaggcactgc 60 ccgccaagga gccaccagga cagcttcact gaggggaaca cacgcaggac aggagcagag 120 cggagtgggt atcaccccag ctggagacgc cacctcacac gacggcctct ttcctgagtt 180 tatctcccct ttactcgcag atgagagcaa g 211 <210> 10 <211> 218 <212> DNA <213> Canis familiaris <400> 10 tcctttggct agttcccacg tgccttgtgt ttttccatct tcctgatcac ggccgtagct 60 gcagtcttca aacctgctca gaggccactg cccaccttgt ctctaccctg ctctcatcgc 120 attggggtac tctcgtggga ggtgctgagg gcttctgaag acccctaggg aggcttcctt 180 gtaaactgaa gaggagacct ttaatcattt cgacctcc 218 <210> 11 <211> 223 <212> DNA <213> Canis familiaris <400> 11 tggtttagat tctttatttg ttttatttta atgaccttct gaatcattca tttttctact 60 tctgaacaga ttcacttttg gccacttcct tgtatagaaa tccaaacctc cctttaaaac 120 tcagcaccaa caaccccctt ctcccaaaaa ttctcatcta taccattccc tcttcaggaa 180 gaagtattcc cctccccact ctttgtacca ttcatctggt att 223 <210> 12 <211> 280 <212> DNA <213> Canis familiaris <400> 12 gcccagggca tgatcctgga gtcccaaaat taagtcccac attgggctcc ctgtgtggag 60 cctgcttctc cctctgcctc tctctctctc tctctctctc tctctttctc tcactctctg 120 tgtctctcat gaataaataa aaaaaaatcc ttaaaaaaag aaaagaaaaa tatcttttac 180 attgttcgaa gaccactaat tttaaaagaa taacattaga gaaaatgcta cttggctttt 240 ctttgatgat atttcccctc catgttataa ttttgaatgc 280 <210> 13 <211> 219 <212> DNA <213> Canis familiaris <400> 13 gctgtttgca cataactatt ttagcatcct gtttctatct tagagatatc ccagattgga 60 aaataatggt cagtaaattg agaaggaaaa aaatggcagc ccacacacac tcggatctgt 120 ccgctcatga gtgtttcatg cattcctctc atcttatttc ttgtcctctg tcctccaaga 180 aaaatagttg tctctgttgg ctacactaga cccttgtgc 219 <210> 14 <211> 214 <212> DNA <213> Canis familiaris <400> 14 aacttcttca gcttcgggga gatgttaaat tccaagactc cttcactatc ctaaagaaac 60 agcaataaaa tgtgtttcag gattcaattc cttcagcttc agaagctgag acggatgaac 120 tagtttgggg gaaatgagac atgacccaac ccttcaccta aacaaaaatg actccaaatt 180 gaacttttcg caaagttcac catcctatgt gata 214 <210> 15 <211> 252 <212> DNA <213> Canis familiaris <400> 15 ccctgtggga tggagtccca catcgggttc cgcgcaggga gcctgcttcc ccctctgcct 60 gtgtctctca tgaataaata aatgaaatct taaaaaaaaa aaagaaaata gatggtaaaa 120 tattgtacac aatggccatg tgggcgctgg ttgttgatag tccatgaact tgacgccttc 180 tgggagaagg agaagcctgg atacgcttct ctctgccctc tgaagctgca ttaaataaaa 240 cccagctcag at 252 <210> 16 <211> 245 <212> DNA <213> Canis familiaris <400> 16 ggctccatgc agggagcctg acatgggact cgatcctggg tctccagaat caggccctgg 60 gctgaaggtg gcactaaacc actgagccac ccgggctgcc ctggaggatt ttccagacca 120 ggagagaacc ggagcatgag tggtcctgtt gaccggcgaa ggagaagagg aggatttgat 180 ggtggaggca tgagcagagg tgggcagaga ggaggataca gtggaatggg cagcgctgga 240 gagcc 245 <210> 17 <211> 217 <212> DNA <213> Canis familiaris <400> 17 tttgctgtat gactcaactc tggacacctc tgtttaactc atgcatgtgc tgcttcttcc 60 taggatattc actggctcat ctggctttct caccctcaag taaaataaag tctcgtggcc 120 atgacttgct caacaatttt ccatgttagc caggtaatat agaggctcag aggtctctgc 180 actgacatca gctctacttc caggaatgaa aaagaaa 217 <210> 18 <211> 317 <212> DNA <213> Canis familiaris <400> 18 gcacacaggc ttacaatttt aataggtatt gccgtatcat tttcaagaga ggttatggtt 60 ataccagttt atacttttac caagagtact tgtttacctc acttttgtca acatttatca 120 tcaggcttga gtttttgcca gtgtgaatgg gtaaatggta gaagttcatt gttttagtgt 180 ctctcagatt gatagcattt tatatgttag gccttctctt ctgtgaattg cctatttgtg 240 ttcgttcttc attttcctat tggattctta gtcttggaac ccaacacaat aggaatattt 300 gttacagatc ttttctt 317 <210> 19 <211> 213 <212> DNA <213> Canis familiaris <400> 19 ggaaaatggt cagatctccc ctgatggctt cttgtcaaaa tctgctccac cagagcttat 60 gaatatggcg ggagatggca ttccccacaa ccaaatggat tctctgtcag atgacttcac 120 taccctaagg aaagatggcc tgattcccaa acctggtact aacacacttc taggaggaag 180 caaaaagtgc agtgtctctg tcgaggatca gaa 213 <210> 20 <211> 219 <212> DNA <213> Canis familiaris <400> 20 atctttccaa gtgtgtgacc ttcggtggct tctgccattc tagctgcaga gtccttctcg 60 tgttctgctt gccgaactct gtgttcccgt cattctgttc acatagccgc tgcctggcac 120 gggagcgcat cacttgcctt caagagcttt ggaagcggtc acttgtgctc cttgagcgtc 180 agctgttgta ggtggaccct tggcccctcc attgacctg 219 <210> 21 <211> 229 <212> DNA <213> Canis familiaris <400> 21 ttgggcatca ctgtcatgaa ctagaagaga gaaatgaata aatctatctc attattccat 60 ttagggctcc ctattgccaa cactgaagta aagtgatgct gacctgtgac cttttaattg 120 cttcccctag aatatatcag cccataaatt ttgtgaaaag gaagaaattg ccctgtagag 180 tgtctccttc agtggtgaaa tggcattcat agaggaggac tagcctgta 229 <210> 22 <211> 247 <212> DNA <213> Canis familiaris <400> 22 tctttgaact ccactttctg tactaataaa atgaagacaa taaatctatc ttgcagcatg 60 tttatgaaga ttaaatgtgc acattttcct aaagcatgga gaaactattt tctagatatg 120 ttaatgggta gttggtgcct atgtatgtga atcaggaaga gtaccatgat ctaaagattt 180 ctgaaaataa tgaagttatt gtatttgtag tcttacacac caacttctca gtctatcgtg 240 aagtcta 247 <210> 23 <211> 212 <212> DNA <213> Canis familiaris <400> 23 tggggtgggt acgttttaca aaaagaaaac aacaacaaca ccctcccccc aatcccaacc 60 ggttaaaaca agtaaaatgg cagatctcaa aaaacatttg ggaagcagtg gaccagtcgg 120 taaataccag aacaggcatt aaaataaccc aggtcaggta ccgagaggta taaattcttg 180 actcatcttc catggatctg tatttaaata ca 212 <210> 24 <211> 255 <212> DNA <213> Canis familiaris <400> 24 tcctgtgcag agggacacgt gaaggcccta ggtcctcctg ggagaaaaga tttccctcct 60 aatgatccag ggactaggat ttcattctga aatggaatgg agaatggcag gtgtggcttt 120 ctggggattg agaaccacag gccccaggag attcaggaaa ggacagtaat gccctgctgc 180 tcaggccccg gtggaggaat catatcctca gctcagcaac accacccgcc cccctacggc 240 cccgaggaaa ggcac 255 <210> 25 <211> 217 <212> DNA <213> Canis familiaris <400> 25 gcattgggaa ggtaaggtgg ggcagaggct ccaatttctt ttccatttcc tgtatattct 60 gcactgcttt cagtgtttta attgattaca tcaactgtgc tcatttccct ggacaaattg 120 gcctttacac agaagaggca attacctggg cttgttccat cccaatcagc agagcaggca 180 ggagcctctt tggggcccca caagattata ttatctg 217 <110> REPUBLIC OF KOREA (MANAGEMENT: RURAL DEVELOPMENT ADMINISTRATION) <120> SNP for diagnosing hip dysplasia in dog and uses <130> PN10191 <160> 25 <170> KopatentIn 1.71 <210> 1 <211> 212 <212> DNA (213) Canis familiaris <400> 1 aaagatccct gtagtccagg gtcactgcaa ctgcaacaga caggcttggg acagacatct 60 gatctgacta cagtcctcac ccactaacaa aatcctctca gggattttgg agcacaggaa 120 gagtgctcca cagtcctgga aaatgagcaa agagtatcta gtctgaccta actacaagcc 180 tcaggtggct ctgattagct tcttaacaaa ac 212 <210> 2 <211> 267 <212> DNA (213) Canis familiaris <400> 2 tttagtggct ctgaacaacc taccatggct ttcgaagaaa atcagctgtg gtcccaagga 60 catttgaaac ttgggcaaag taccaagaaa aggcttatga gggaggcatt gttttggggc 120 gtcttatagc ttggaatcat tatctgcgaa tgaaagttag aagaaagatt tcagcttatt 180 taaagaactt tccattagtc aaaaccatct atagatgaaa caaacacttt tttataaaag 240 aatgaatttc tcattcttta gggcatt 267 <210> 3 <211> 235 <212> DNA (213) Canis familiaris <400> 3 gcagaagttt ctgtgtaagc gccaatccca gttcctgttt atcaccctgc cctagcttat 60 tcgttgttcc ccttacttgc agccgcttta cggtgtaata cgtgtctggc tgcctgtccg 120 tgcagccacc tgaatgtctc tttttggaga aagacagggg tagaagctct gtagcaactg 180 aactctttaa agatttgtat ttatttgaaa gagacagaga gagagagggg cgggg 235 <210> 4 <211> 211 <212> DNA (213) Canis familiaris <400> 4 aggccaggaa tggaagccag tgggtggtga gcatatggga aacagagggc ccacattctc 60 agaagagtga gggagctggg gtgggagtga cagttcaggg tgctgccacg ggaaacagtg 120 gggccatgat gggattctgc tggcccgttg ggagagggtc acctgggtta attaaaaggg 180 tgtccgagtc ctgggaagct tcctccctcc c 211 <210> 5 <211> 257 <212> DNA (213) Canis familiaris <400> 5 ttgttagggg ttccaggtac tcctaggaga aactgccaac tctatgttga gatgaaacta 60 gcacaaccct ggcagggaga tgcagggtgc caaccaaccc ctccacagta tagtttaaca 120 gagaaagctg tggctccagg aaaggaaagg ggtgacccct taccacctat tgtgctgtag 180 ggccctagcc cttatctgct ctcttccagg agcatctgct agaacaaaca gaaactcctc 240 tccccgtatc ctcctgt 257 <210> 6 <211> 262 <212> DNA (213) Canis familiaris <400> 6 gaaagttcag gcttttgtgg gaaagaaacc agatcaacaa catggacttt agggaggtga 60 gaaaataacc actctgggta gtaatatccc ctttggacaa actagactga gagaagccca 120 gggaagtgtt agaatagttt tcagccttga ctggatcaga atcacttgtg gatttttcta 180 aatattttat tcattcatct ctctcacaca cacacaggca gagacataag cagagggaga 240 agcaggctcc ccatggaact tg 262 <210> 7 <211> 211 <212> DNA (213) Canis familiaris <400> 7 cccttatccc catcccatcc agccacatcc aaatgatttt aatatattgt ttaggttaaa 60 ccatccagtt aaaggctaat gcagatctgg gaaggatcag gaaacaagag aaagtgaagg 120 agtgccaagg aaagagttgg tggaagtctg gaggggaaat tagttataaa tgtcaagttg 180 gaagtctaga ggagataaaa aggcagagtg t 211 <210> 8 <211> 216 <212> DNA (213) Canis familiaris <400> 8 gatcagttct catctccttc tttaggtatc taggagatct tgggatgcca atcaggtgtt 60 tgtatctgac tcaacctttc tatgctttac tccccagtat gtgaaatcgt tttcataagg 120 agaggaactt tctgtgggcc acataaacaa agaaacccag aaacagggtt cagcctggag 180 aggagagatt atgattgggg tatcaggact cagggg 216 <210> 9 <211> 211 <212> DNA (213) Canis familiaris <400> 9 ttggtctacc agcagatgac agcggacagg agcccctagg gctggggttg gaggcactgc 60 ccgccaagga gccaccagga cagcttcact gaggggaaca cacgcaggac aggagcagag 120 cggagtgggt atcaccccag ctggagacgc cacctcacac gacggcctct ttcctgagtt 180 tatctcccct ttactcgcag atgagagcaa g 211 <210> 10 <211> 218 <212> DNA (213) Canis familiaris <400> 10 tcctttggct agttcccacg tgccttgtgt ttttccatct tcctgatcac ggccgtagct 60 gcagtcttca aacctgctca gaggccactg cccaccttgt ctctaccctg ctctcatcgc 120 attggggtac tctcgtggga ggtgctgagg gcttctgaag acccctaggg aggcttcctt 180 gtaaactgaa gaggagacct ttaatcattt cgacctcc 218 <210> 11 <211> 223 <212> DNA (213) Canis familiaris <400> 11 tggtttagat tctttatttg ttttatttta atgaccttct gaatcattca tttttctact 60 tctgaacaga ttcacttttg gccacttcct tgtatagaaa tccaaacctc cctttaaaac 120 tcagcaccaa caaccccctt ctcccaaaaa ttctcatcta taccattccc tcttcaggaa 180 gaagtattcc cctccccact ctttgtacca ttcatctggt att 223 <210> 12 <211> 280 <212> DNA (213) Canis familiaris <400> 12 gcccagggca tgatcctgga gtcccaaaat taagtcccac attgggctcc ctgtgtggag 60 cctgcttctc cctctgcctc tctctctctc tctctctctc tctctttctc tcactctctg 120 tgtctctcat gaataaataa aaaaaaatcc ttaaaaaaag aaaagaaaaa tatcttttac 180 attgttcgaa gaccactaat tttaaaagaa taacattaga gaaaatgcta cttggctttt 240 ctttgatgat atttcccctc catgttataa ttttgaatgc 280 <210> 13 <211> 219 <212> DNA (213) Canis familiaris <400> 13 gctgtttgca cataactatt ttagcatcct gtttctatct tagagatatc ccagattgga 60 aaataatggt cagtaaattg agaaggaaaa aaatggcagc ccacacacac tcggatctgt 120 ccgctcatga gtgtttcatg cattcctctc atcttatttc ttgtcctctg tcctccaaga 180 aaaatagttg tctctgttgg ctacactaga cccttgtgc 219 <210> 14 <211> 214 <212> DNA (213) Canis familiaris <400> 14 aacttcttca gcttcgggga gatgttaaat tccaagactc cttcactatc ctaaagaaac 60 agcaataaaa tgtgtttcag gattcaattc cttcagcttc agaagctgag acggatgaac 120 tagtttgggg gaaatgagac atgacccaac ccttcaccta aacaaaaatg actccaaatt 180 gaacttttcg caaagttcac catcctatgt gata 214 <210> 15 <211> 252 <212> DNA (213) Canis familiaris <400> 15 ccctgtggga tggagtccca catcgggttc cgcgcaggga gcctgcttcc ccctctgcct 60 gtgtctctca tgaataaata aatgaaatct taaaaaaaaa aaagaaaata gatggtaaaa 120 tattgtacac aatggccatg tgggcgctgg ttgttgatag tccatgaact tgacgccttc 180 tgggagaagg agaagcctgg atacgcttct ctctgccctc tgaagctgca ttaaataaaa 240 cccagctcag at 252 <210> 16 <211> 245 <212> DNA (213) Canis familiaris <400> 16 ggctccatgc agggagcctg acatgggact cgatcctggg tctccagaat caggccctgg 60 gctgaaggtg gcactaaacc actgagccac ccgggctgcc ctggaggatt ttccagacca 120 ggagagaacc ggagcatgag tggtcctgtt gaccggcgaa ggagaagagg aggatttgat 180 ggtggaggca tgagcagagg tgggcagaga ggaggataca gtggaatggg cagcgctgga 240 gagcc 245 <210> 17 <211> 217 <212> DNA (213) Canis familiaris <400> 17 tttgctgtat gactcaactc tggacacctc tgtttaactc atgcatgtgc tgcttcttcc 60 taggatattc actggctcat ctggctttct caccctcaag taaaataaag tctcgtggcc 120 atgacttgct caacaatttt ccatgttagc caggtaatat agaggctcag aggtctctgc 180 actgacatca gctctacttc caggaatgaa aaagaaa 217 <210> 18 <211> 317 <212> DNA (213) Canis familiaris <400> 18 gcacacaggc ttacaatttt aataggtatt gccgtatcat tttcaagaga ggttatggtt 60 ataccagttt atacttttac caagagtact tgtttacctc acttttgtca acatttatca 120 tcaggcttga gtttttgcca gtgtgaatgg gtaaatggta gaagttcatt gttttagtgt 180 ctctcagatt gatagcattt tatatgttag gccttctctt ctgtgaattg cctatttgtg 240 ttcgttcttc attttcctat tggattctta gtcttggaac ccaacacaat aggaatattt 300 gttacagatc ttttctt 317 <210> 19 <211> 213 <212> DNA (213) Canis familiaris <400> 19 ggaaaatggt cagatctccc ctgatggctt cttgtcaaaa tctgctccac cagagcttat 60 gaatatggcg ggagatggca ttccccacaa ccaaatggat tctctgtcag atgacttcac 120 taccctaagg aaagatggcc tgattcccaa acctggtact aacacacttc taggaggaag 180 caaaaagtgc agtgtctctg tcgaggatca gaa 213 <210> 20 <211> 219 <212> DNA (213) Canis familiaris <400> 20 atctttccaa gtgtgtgacc ttcggtggct tctgccattc tagctgcaga gtccttctcg 60 tgttctgctt gccgaactct gtgttcccgt cattctgttc acatagccgc tgcctggcac 120 gggagcgcat cacttgcctt caagagcttt ggaagcggtc acttgtgctc cttgagcgtc 180 agctgttgta ggtggaccct tggcccctcc attgacctg 219 <210> 21 <211> 229 <212> DNA (213) Canis familiaris <400> 21 ttgggcatca ctgtcatgaa ctagaagaga gaaatgaata aatctatctc attattccat 60 ttagggctcc ctattgccaa cactgaagta aagtgatgct gacctgtgac cttttaattg 120 cttcccctag aatatatcag cccataaatt ttgtgaaaag gaagaaattg ccctgtagag 180 tgtctccttc agtggtgaaa tggcattcat agaggaggac tagcctgta 229 <210> 22 <211> 247 <212> DNA (213) Canis familiaris <400> 22 tctttgaact ccactttctg tactaataaa atgaagacaa taaatctatc ttgcagcatg 60 tttatgaaga ttaaatgtgc acattttcct aaagcatgga gaaactattt tctagatatg 120 ttaatgggta gttggtgcct atgtatgtga atcaggaaga gtaccatgat ctaaagattt 180 ctgaaaataa tgaagttatt gtatttgtag tcttacacac caacttctca gtctatcgtg 240 aagtcta 247 <210> 23 <211> 212 <212> DNA (213) Canis familiaris <400> 23 tggggtgggt acgttttaca aaaagaaaac aacaacaaca ccctcccccc aatcccaacc 60 ggttaaaaca agtaaaatgg cagatctcaa aaaacatttg ggaagcagtg gaccagtcgg 120 taaataccag aacaggcatt aaaataaccc aggtcaggta ccgagaggta taaattcttg 180 actcatcttc catggatctg tatttaaata ca 212 <210> 24 <211> 255 <212> DNA (213) Canis familiaris <400> 24 tcctgtgcag agggacacgt gaaggcccta ggtcctcctg ggagaaaaga tttccctcct 60 aatgatccag ggactaggat ttcattctga aatggaatgg agaatggcag gtgtggcttt 120 ctggggattg agaaccacag gccccaggag attcaggaaa ggacagtaat gccctgctgc 180 tcaggccccg gtggaggaat catatcctca gctcagcaac accacccgcc cccctacggc 240 cccgaggaaa ggcac 255 <210> 25 <211> 217 <212> DNA (213) Canis familiaris <400> 25 gcattgggaa ggtaaggtgg ggcagaggct ccaatttctt ttccatttcc tgtatattct 60 gcactgcttt cagtgtttta attgattaca tcaactgtgc tcatttccct ggacaaattg 120 gcctttacac agaagaggca attacctggg cttgttccat cccaatcagc agagcaggca 180 ggagcctctt tggggcccca caagattata ttatctg 217
Claims (7)
서열번호 1 내지 25 중에서 선택되는 하나 이상의 폴리뉴클레오티드의 각 SNP 위치 염기인 다형성 부위의 유전자형을 결정하는 단계를 포함하는 개 고관절 이형성증의 조기 진단 방법.Separating the nucleic acid sample from the subject, and
A method for early diagnosis of canine hip dysplasia comprising determining the genotype of a polymorphic site, each SNP position base of at least one polynucleotide selected from SEQ ID NOs: 1-25.
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KR102124770B1 (en) * | 2018-12-12 | 2020-06-19 | 대한민국 | Composition for early predicting or diagnosing hip dysplasia in dog |
KR102194878B1 (en) * | 2019-10-08 | 2020-12-23 | 대한민국 | Composition for early predicting or diagnosing mental stability in dog |
KR102194881B1 (en) * | 2019-10-11 | 2020-12-24 | 대한민국 | SNP marker for prediction of dog's obesity and prediction method using the same |
WO2023140409A1 (en) * | 2022-01-20 | 2023-07-27 | 주식회사 엠케이바이오텍 | Composition for treating canine hip dysplasia using prime editor |
KR102472344B1 (en) * | 2022-05-31 | 2022-11-30 | 주식회사 엠케이바이오텍 | Composition for treating alleviated hip dysplasia of dog using prime editors |
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