WO2019159884A1 - 認知症の検出のためのキット又はデバイス及び方法 - Google Patents
認知症の検出のためのキット又はデバイス及び方法 Download PDFInfo
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
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- C—CHEMISTRY; METALLURGY
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12Q2600/00—Oligonucleotides characterized by their use
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Definitions
- the present invention relates to a kit or device for detecting dementia comprising a nucleic acid capable of specifically binding to a specific miRNA or a complementary strand thereof, which is used for examining the presence or absence of dementia in a subject, and
- the present invention relates to a method for detecting dementia, which includes measuring the expression level of miRNA.
- the cost of medical care and care for patients with dementia will be ⁇ 14.500 billion in 2014 (breakdown: medical expenses ⁇ 1.9 trillion (hospitalization ⁇ 9703 billion, outpatient ⁇ 941.2 billion), nursing care costs 6 It has been reported that the amount has risen to 4 trillion yen (about 3,58.1 billion yen at home, about 2,916 billion yen for facilities) and informal care cost 6,200 billion yen (Ministry of Health, Labor and Welfare, Research Team “ Estimated social cost of dementia, May 2015). Worldwide, the number of patients with dementia will increase to 74.7 million by 2030, and the cost of medical care for dementia will be as high as 240 trillion yen (ADI “World Alzheimer Report 2015”). Dementia is generally progressive and involves irreversible degeneration of brain neurons. In order to reduce the burden on patients and caregivers and social costs at present when there are no drugs for the treatment of dementia, it is important to examine and diagnose dementia and to provide early medical intervention to suppress progression.
- dementia is diagnosed by differential diagnosis such as medical history, current symptoms, physical findings, neuropsychological tests, blood tests, and imaging tests.
- MMSE Mini-Mental State Test
- the blood test recommended in the Dementia Diagnostic Disease Guidelines is necessary for excluding internal diseases that cause dementia and dementia-like symptoms in the diagnosis of degenerative dementia such as Alzheimer-type dementia.
- degenerative dementia such as Alzheimer-type dementia.
- Low cerebrospinal fluid (CSF) cerebral spinal fluid amyloid protein concentration and high tau concentration in Alzheimer type dementia are being utilized as surrogate markers, but there is a problem of high patient invasiveness.
- CSF cerebrospinal fluid
- MCI mild cognitive dysfunction
- MiR-483-5p miRNA-483-5p
- miR-486-5p miR-30b-5p
- miR-200a-3p miR-502-3p
- miR-142-3p miRNA-142-3p
- MCI mild cognitive dysfunction
- a dementia marker search was attempted by ingesting supplements that alleviate dementia symptoms in subjects with mild dementia, and comparing serum miRNA expression before and after ingestion.
- Patent Document 2 reports that this antisense strand increases levels of nerve growth factor BDNF and IGF-1 and regenerates synapses in Alzheimer's disease model mice, and reports that this marker was also applicable to diagnosis. Yes.
- Alzheimer's disease is measured by measuring the miRNA expression levels of 67 species (hsa-miR-1296, hsa-miR-424 *, hsa-miR-424, hsa-miR-629, etc.) in the specimen There is a report that this can be diagnosed (Patent Document 3).
- Patent document 5 aims at the treatment and prevention of Alzheimer's disease and neurofibrillary degeneration due to abnormal tau expression, and the therapeutic purpose obtained as a result of searching for miRNA that binds to the 3′UTR of tau mRNA and controls tau expression. It is reported that markers (miR-185-5p, miR-151-5p, etc.) were applicable to diagnosis.
- Patent Document 7 relates to cancer, inflammatory diseases, and dementia in body fluids including blood, serum, and plasma as an example of detection for the purpose of developing a microfluidic device that hybridizes and detects microRNA. It is reported that microRNA was detected.
- dementia may have many disease types.
- the result of pathological diagnosis was Alzheimer's dementia. Only 14 (3.13%) included 366 (81.88%) who had vascular dementia and Lewy body dementia in addition to Alzheimer's dementia.
- Non-Patent Document 2 a dementia different from Alzheimer type dementia such as vascular dementia, Lewy body dementia, hippocampal atrophy.
- JP 2017-184642 A US Patent Application Publication No. 2013/0184331 US Patent Application Publication No. 2014/0206777 US Patent Application Publication No. 2014/0120545 US Patent Application Publication No. 2017/0002348 International Publication No. 2017/084770 International Publication No. 2017/059094
- Non-Patent Document 1 and Patent Documents 1 to 7 cannot be said to have sufficient performance as a marker for diagnosis of dementia as described below.
- Non-Patent Document 1 only early-stage Alzheimer-type dementia and Alzheimer-type dementia included in mild dementia (MCI) are verified, and it is unclear whether dementia disease types other than Alzheimer-type dementia can be detected. is there.
- Patent Document 1 only MCI, which is a stage before dementia, has been verified, and it is unknown whether dementia can be detected.
- Patent Document 2 only Alzheimer model mice and human brain specimens have been verified, and there is no verification with blood specimens that can be collected with minimal invasiveness.
- Patent Document 3 only Alzheimer type dementia is targeted, and it is unclear whether dementia disease types other than Alzheimer type dementia can be detected.
- Patent Document 4 although MCI and a healthy person can be distinguished from MCI and Alzheimer's dementia, it is not possible to distinguish between a healthy person and Alzheimer's dementia.
- Patent Document 5 only verification using a brain tissue is performed as an example, and it is unclear whether a blood sample can be detected in the same manner.
- Patent Document 6 only whether or not the marker is expressed in the microglial cells of the model mouse has been verified, and it is unclear whether the marker can be detected using a human blood sample.
- Patent Document 7 relates to a diagnostic device using microRNA in a body fluid, and dementia is exemplified together with cancer and inflammatory diseases. Although there is a description of detection of microRNA using specimens including blood, serum, and plasma, there is no example, and it is unclear whether the marker can be detected using human blood specimens.
- cerebrospinal fluid as a sample for measurement is not preferable because it is highly invasive to patients and can be detected using a blood sample that can be collected in a minimally invasive manner.
- a comprehensive dementia marker that can be used is desired. In particular, if the dementia can be detected without omission, the progression of dementia can be expected by medical intervention.
- An object of the present invention is to provide a dementia marker capable of diagnosing one or more dementia disease types capable of distinguishing between dementia and normal cognitive function (non-dementia), and a nucleic acid capable of specifically binding to the marker. It is to provide a method that can be used to objectively and effectively detect whether or not the disease is dementia. Specifically, 1. There is no difference between medical facilities and doctors. 2. Comprehensive detection of multiple types of dementia. 3. Sensitivity / specificity of dementia is high. An object of the present invention is to provide an inspection method that satisfies one or more, preferably all of the four points of low invasiveness.
- the present inventors have selected one of Alzheimer type dementia, vascular dementia, Lewy body dementia, normal pressure hydrocephalus, frontotemporal lobar degeneration, and the like.
- the present inventors have found a novel dementia marker that can detect dementia of the above-mentioned disease types, and have completed the present invention.
- the present invention includes the following aspects. (1) Dementia markers miR-4274, miR-4272, miR-4728-5p, miR-4443, miR-4506, miR-6773-5p, miR-4662a-5p, miR-3184-3p, miR -4281, miR-320d, miR-6729-3p, miR-5192, miR-6683-5p, miR-1234-3p, miR-1233-3p, miR-4539, miR-3914, miR-4438-5p, miR -548 au-3p, miR-1539, miR-4720-3p, miR-365b-5p, miR-4486, miR-1227-5p, miR-4667-5p, miR-6088, miR-6820-5p, miR-4505 , MiR-548q, miR-4658, mi -450a-5p, miR-1260b, miR-3777-5p, miR-6777-3p
- polynucleotide according to any one of the following (a) to (e): (A) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOs: 1-210, 374, 1315-1350, and 1435-1448, or a base sequence in which u is t in the base sequence, variants thereof, A derivative, or a fragment thereof comprising 15 or more consecutive bases, (B) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 1-210, 374, 1315-1350, and 1435-1448, (C) a polynucleotide comprising a base sequence represented by any one of SEQ ID NOs: 1-210, 374, 1315-1350 and 1435-1448 or a base sequence complementary to the base sequence in which u is t in the base sequence A variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive bases, (D) a polynucleotide comprising the
- the kit is another dementia marker, miR-1471, miR-1538, miR-449b-3p, miR-1976, miR-4268, miR-4279, miR-3620-3p, miR-3944 -3p, miR-3156-3p, miR-3187-5p, miR-4687-3p, miR-4695-3p, miR-4697-3p, miR-4713-5p, miR-4723-3p, miR-371b-3p MiR-3151-3p, miR-3192-3p, miR-6728-3p, miR-6736-3p, miR-6740-3p, miR-6741-3p, miR-6743-3p, miR-6747-3p, miR -6750-3p, miR-6754-3p, miR-6759-3p, m R-6761-3p, miR-6762-3p, miR-6769a-3p, miR-6766-3p, miR-6778-3p, miR-6679-3p, miR-6
- polynucleotide according to any one of the following (p) to (t): (P) comprising a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 375 to 390 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or 15 or more consecutive bases Its fragments, (Q) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 375 to 390, (R) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 375 to 390 or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 or more A fragment thereof containing a continuous base of (S) a nucleotide sequence represented by any of SEQ ID NOs: 375 to 390 or
- kits for detecting or predicting dementia further comprising one or more polynucleotides selected from the above, or a nucleic acid II capable of specifically binding to a complementary strand of the polynucleotide.
- polynucleotide according to any one of the following (u) to (y): (U) any of SEQ ID NOs: 3, 8, 15, 26, 34, 40, 53, 69, 99, 101, 107, 109, 112, 125, 128, 133, 191 to 194, 212, and 250 to 374
- a polynucleotide comprising the nucleotide sequence represented by or a nucleotide sequence wherein u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive bases, (V) any of SEQ ID NOs: 3, 8, 15, 26, 34, 40, 53, 69, 99, 101, 107, 109, 112, 125, 128, 133, 191 to 194, 212, and 250 to 374 (W) SEQ ID NOs: 3, 8, 15, 26, 34, 40, 53, 69, 99, 101, 107, 109, 112, 125, 128, 133, 191 to A polynu
- the device is another dementia marker, miR-1471, miR-1538, miR-449b-3p, miR-1976, miR-4268, miR-4279, miR-3620-3p, miR-3944 -3p, miR-3156-3p, miR-3187-5p, miR-4687-3p, miR-4695-3p, miR-4697-3p, miR-4713-5p, miR-4723-3p, miR-371b-3p MiR-3151-3p, miR-3192-3p, miR-6728-3p, miR-6736-3p, miR-6740-3p, miR-6741-3p, miR-6743-3p, miR-6747-3p, miR -6750-3p, miR-6754-3p, miR-6759-3p miR-6676-3p, miR-6762-3p, miR-6769a-3p, miR-6766-3p, miR-6778-3p, miR-6679-3p, miR-6786-3
- the device according to any one of (16) The polynucleotide according to any one of the following (k) to (o): (K) including a polynucleotide comprising the nucleotide sequence represented by any of SEQ ID NOs: 250 to 373 or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 or more consecutive bases Its fragments, (L) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 250 to 373, (m) the base sequence represented by any of SEQ ID NOs: 250 to 373 or a base in which u is t in the base sequence A polynucleotide comprising a base sequence complementary to the sequence, a variant thereof, a derivative thereof, or a fragment thereof containing 15 or more consecutive bases, (N) a polynucleotide comprising a nucleotide sequence represented by any of SEQ ID NO
- a device for detecting or predicting dementia which further comprises one or more polynucleotides selected from the above, or a nucleic acid II that can specifically bind to a complementary strand of the polynucleotide.
- polynucleotide according to any one of the following (u) to (y): (U) any of SEQ ID NOs: 3, 8, 15, 26, 34, 40, 53, 69, 99, 101, 107, 109, 112, 125, 128, 133, 191 to 194, 212, and 250 to 374
- a polynucleotide comprising the nucleotide sequence represented by or a nucleotide sequence wherein u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive bases, (V) any of SEQ ID NOs: 3, 8, 15, 26, 34, 40, 53, 69, 99, 101, 107, 109, 112, 125, 128, 133, 191 to 194, 212, and 250 to 374 (W) SEQ ID NOs: 3, 8, 15, 26, 34, 40, 53, 69, 99, 101, 107, 109, 112, 125, 128, 133, 191 to A polynu
- the expression level of the polynucleotide is measured using a nucleic acid that can specifically bind to the polynucleotide or a complementary strand of the polynucleotide, and the nucleic acid is any of the following (a) to (e): Polynucleotides shown in: (A) a polynucleotide comprising the base sequence represented by any one of SEQ ID NOS: 1-210, 374, 1315-1350, and 1435-1448, or the base sequence in which u is t in the base sequence, or a variant thereof A derivative thereof, or a fragment thereof comprising 15 or more consecutive bases, (B) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 1-210, 374, 1315-1350, and 1435-1448, (C) Comprising a base sequence complementary to the base sequence represented by any of SEQ ID NOS: 1-210, 374, 1315-1350, and 1435-1448, or
- the expression level of the polynucleotide is measured using a nucleic acid that can specifically bind to the polynucleotide or a complementary strand of the polynucleotide, and the nucleic acid is any of the following (f) to (j): Polynucleotides shown in: (F) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 211 to 249, 1351 to 1356, and 1449 to 1453, or the base sequence in which u is t in the base sequence, a variant thereof, A derivative, or a fragment thereof comprising 15 or more consecutive bases, (G) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 211 to 249, 1351 to 1356, and 1449 to 1453, (H) a polynucleotide comprising a base sequence complementary to the base sequence represented by any one of SEQ ID NOs: 211 to 249, 1351 to 13
- the expression level of the polynucleotide is measured using a nucleic acid capable of specifically binding to the polynucleotide or a complementary strand of the polynucleotide, and the nucleic acid is any of the following (k) to (o) Polynucleotides shown in: (K) including a polynucleotide comprising the nucleotide sequence represented by any of SEQ ID NOs: 250 to 373 or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 or more consecutive bases Its fragments, (L) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 250 to 373, (m) the base sequence represented by any of SEQ ID NOs: 250 to 373 or a base in which u is t in the base sequence A polynucleotide comprising a base sequence complementary to the sequence, a variant thereof, a
- the expression level of the polynucleotide is measured using a nucleic acid capable of specifically binding to the polynucleotide or a complementary strand of the polynucleotide, and the nucleic acid is any of the following (p) to (t) Polynucleotides shown in: (P) comprising a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 375 to 390 or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or 15 or more consecutive bases Its fragments, (Q) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 375 to 390, (R) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 375 to 390 or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the nucleot
- MiR-532-3p, miR-877-3p, miR-1238-3p, miR-3130-5p, miR-4298, miR-4290, miR-3943, miR-346, and miR-767-3p Measuring the expression level of one or more polynucleotides II selected from Using the measured expression level to assess in vitro whether or not the subject suffers from dementia, or predict the likelihood that the subject will suffer from dementia or in vitro Dementia detection or prediction method.
- the expression level of the polynucleotide I is measured using a nucleic acid that can specifically bind to the polynucleotide I or a complementary strand of the polynucleotide, and the nucleic acid is represented by the following (u) to (y):
- a polynucleotide comprising the nucleotide sequence represented by or a nucleotide sequence wherein u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or a fragment thereof comprising 15 or more consecutive bases, (V) any of SEQ ID NOs: 3, 8, 15, 26, 34, 40, 53, 69, 99, 101, 107, 109, 112, 125, 128,
- polynucleotide according to any one of the following (a) to (e): (A) a polynucleotide comprising the nucleotide sequence represented by any one of SEQ ID NOS: 194 to 210, 374, and 1315 to 1350, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 Its fragments containing the above consecutive bases, (B) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 194 to 210, 374, and 1315 to 1350, (C) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 194 to 210, 374, and 1315 to 1350, or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the nucleotide sequence, or a variant thereof
- polynucleotide according to any one of the following (f) to (j): (F) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 211 to 212 and 1351-1356, or a base sequence in which u is t in the base sequence, a variant thereof, a derivative thereof, or 15 or more Its fragments containing consecutive bases, (G) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 211-212 and 1351-1356, (H) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 211 to 212 and 1351-1356, or a nucleotide sequence complementary to a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, A derivative, or a fragment thereof comprising 15 or more consecutive bases, (I) a polynucleotide comprising
- the polynucleotide wherein the nucleic acid is represented by any of the following (f) to (j):
- a method for detecting dementia in a subject comprising substituting the expression level of a target gene in a specimen derived from the subject, thereby evaluating dementia or non-dementia.
- the polynucleotide according to any one of the following (a) to (e): (A) a polynucleotide comprising the nucleotide sequence represented by any one of SEQ ID NOS: 194 to 210, 374, and 1315 to 1350, or a nucleotide sequence in which u is t in the nucleotide sequence, a variant thereof, a derivative thereof, or 15 Its fragments containing the above consecutive bases, (B) a polynucleotide comprising the base sequence represented by any of SEQ ID NOs: 194 to 210, 374, and 1315 to 1350, (C) a polynucleotide comprising a nucleotide sequence represented by any one of SEQ ID NOs: 194 to 210, 374,
- the disease type of dementia is Alzheimer type dementia, vascular dementia, Lewy body dementia, normal pressure hydrocephalus. , Frontotemporal lobar degeneration, neurofibrillary tangle dementia, dementia caused by diseases such as infectious diseases, dementia such as alcoholic dementia or vitamin deficiency dementia, or any mixture of these Type or dementia of unknown or unspecified disease type.
- the dementia marker miR-4274 is hsa-miR-4274, and miR-4272 is hsa-miR-. 4272, miR-4728-5p is hsa-miR-4728-5p, miR-4443 is hsa-miR-4443, miR-4506 is hsa-miR-4506, and miR-6773-5p is hsa-miR-6773-5p, miR-4662a-5p is hsa-miR-4662a-5p, miR-3184-3p is hsa-miR-3184-3p, and miR-4281 is hsa-miR- 4281, miR-320d is hsa-miR-320d, miR 6729-3p is hsa-miR-6729-3p, miR-5192 is hsa-miR
- miR-6810-5p is hsa-miR-6810-5p
- miR-6823-3p is hsa-miR-6823-3p
- miR-6825-3p is hsa-miR-6825- 3R
- miR-6629-3p is hsa-miR-6829-3p
- miR-6683-3p is hsa-miR-6833-3p
- miR-6683-3p is hsa-miR-6683-3p.
- MiR-6780b-3p is hsa-miR-6780b-3p
- miR-6845-3p is hsa-miR-6845-3p
- miR-6862-3p is hsa-miR-6862-3p
- miR-6865-3p is hsa-miR-6865-3p
- miR-6870-3p is sa-miR-6870-3p
- miR-6875-3p is hsa-miR-6875-3p
- miR-6877-3p is hsa-miR-6877-3p
- miR-6879-3p is hsa- miR-6879-3p
- miR-6882-3p is hsa-miR-6882-3p
- miR-6885-3p is hsa-miR-6885-3p
- miR-6886-3p is hsa-miR- 686-3p
- the dementia marker miR-6765-3p is hsa-miR-6765-3p, and miR-6784.
- 5p is hsa-miR-6784-5p
- miR-5698 is hsa-miR-5698
- miR-6778-5p is hsa-miR-6778-5p
- miR-1915-3p is hsa-miR- 1915-3p
- miR-6875-5p is hsa-miR-6875-5p
- miR-1343-5p is hsa-miR-1343-5p
- miR-4534 is hsa-miR-4534
- miR-6861-5p is hsa-miR-6861-5p and miR-4721 is hs -MiR-4721
- miR-6756-5p is hsa-miR-6756-5p
- polynucleotide is used for nucleic acids including RNA, DNA, and RNA / DNA (chimera).
- the DNA includes any of cDNA, genomic DNA, and synthetic DNA.
- the RNA includes total RNA, mRNA, rRNA, miRNA, siRNA, snoRNA, snRNA, non-coding RNA, and synthetic RNA.
- synthetic DNA and “synthetic RNA” are artificially generated using, for example, an automatic nucleic acid synthesizer based on a predetermined base sequence (which may be either a natural sequence or a non-natural sequence). It refers to the prepared DNA and RNA.
- non-natural sequence is intended to be used in a broad sense, and is a sequence (for example, one or more nucleotide substitutions, deletions, insertions and / or additions) that differs from the natural sequence ( That is, it includes a mutant sequence), a sequence containing one or more modified nucleotides (ie, a modified sequence), and the like.
- the polynucleotide is used interchangeably with the nucleic acid.
- a “fragment” is a polynucleotide having a base sequence of a continuous part of a polynucleotide, and desirably has a length of 15 bases or more, preferably 17 bases or more, more preferably 19 bases or more. .
- RNA and double-stranded DNA include not only RNA and double-stranded DNA, but also each single-stranded DNA such as positive strand (or sense strand) or complementary strand (or antisense strand) constituting the same. It is intended to be used.
- the length is not particularly limited.
- “gene” refers to double-stranded DNA including human genomic DNA, single-stranded DNA (positive strand), and single-stranded DNA having a sequence complementary to the positive strand (complementary). Strand), cDNA, microRNA (miRNA), and fragments thereof, the human genome, and transcripts thereof.
- the “gene” is not limited to a “gene” represented by a specific nucleotide sequence (or sequence number), but also RNAs having biological functions equivalent to RNA encoded by these, for example, homologs (ie, homologs). Or an ortholog), variants such as genetic polymorphisms, and “nucleic acids” encoding derivatives.
- nucleic acid encoding such homologue, variant or derivative includes, under stringent conditions described later, SEQ ID NOS: 1-1314, 1315-1434, and 1435-1505 (for example, the sequence 194 to 212, 374, 398, 490, 591, 593 to 609, 766, 1015 to 1017, 1019 to 1024, 1026 to 1031, 1285 to 1286, and 1315 to 1434)
- SEQ ID NOS: 1-1314, 1315-1434, and 1435-1505 for example, the sequence 194 to 212, 374, 398, 490, 591, 593 to 609, 766, 1015 to 1017, 1019 to 1024, 1026 to 1031, 1285 to 1286, and 1315 to 1434
- a “nucleic acid” having a base sequence that hybridizes with a complementary sequence of the base sequence in which u is t in the base sequence can be mentioned.
- the “gene” does not ask whether the functional region is different, and may include, for example, an expression control region, a coding region, an exon, or an intron. Further, the “gene” may be contained in the cell, may be released outside the cell and may be present alone, or may be encapsulated in a vesicle called an exosome.
- exosome or “exosome” is a vesicle encapsulated in a lipid bilayer secreted from a cell. Exosomes are derived from multivesicular endosomes, and when released to the extracellular environment, they may contain biological substances such as “genes” such as RNA and DNA and proteins. It is known that exosomes are contained in body fluids such as blood, serum, plasma and lymph.
- RNA refers to RNA synthesized using a DNA sequence of a gene as a template.
- RNA is synthesized in such a manner that RNA polymerase binds to a site called a promoter located upstream of the gene and ribonucleotides are bound to the 3 'end so as to be complementary to the DNA base sequence.
- This RNA includes not only the gene itself but also the entire sequence from the transcription start point to the end of the poly A sequence, including the expression control region, coding region, exon or intron.
- microRNA is a protein complex that is transcribed as a hairpin-like RNA precursor, cleaved by a dsRNA cleaving enzyme having RNase III cleaving activity, and called RISC. 15-25 base non-coding RNA that is incorporated into and is involved in the translational repression of mRNA.
- miRNA used herein includes not only “miRNA” represented by a specific base sequence (or sequence number) but also a precursor of the “miRNA” (pre-miRNA, pri-miRNA).
- miRNAs that are biologically equivalent to the miRNAs encoded by them, such as homologues (ie, homologs or orthologs), variants such as genetic polymorphisms, and derivatives that encode derivatives.
- homologues ie, homologs or orthologs
- variants such as genetic polymorphisms
- derivatives that encode derivatives.
- the “miRNA” encoding such precursor, homologue, mutant or derivative can be specifically identified by “miRBase” (version 21), and can be sequenced under stringent conditions described later.
- MiRNA having a base sequence that hybridizes with a complementary sequence of any one of the specific base sequences.
- MiRBBase version 21 is a database on the Web that provides miRNA base sequences, annotations, target gene predictions, and the like (http://www.mirbase.org/).
- miRNAs registered in “miRBase” are limited to those that have been cloned or that have been shown to be expressed and processed in vivo.
- the “miRNA” used herein may be a gene product of a miR gene, and such a gene product is a mature miRNA (for example, 15 to 25 involved in the suppression of translation of mRNA as described above. Bases, or 19-25 bases of non-coding RNA) or miRNA precursors (eg, pre-miRNA or pri-miRNA as described above).
- the “probe” includes a polynucleotide used for specifically detecting RNA produced by gene expression or a polynucleotide derived therefrom and / or a polynucleotide complementary thereto.
- the “primer” includes a continuous polynucleotide and / or a complementary polynucleotide that specifically recognizes and amplifies RNA generated by gene expression or a polynucleotide derived therefrom.
- complementary polynucleotide refers to SEQ ID NOs: 1 to 1314, 1315 to 1434, and 1435 to 1505 (for example, SEQ ID NOs: 194 to 212, 374, 398, 490, 591).
- the base sequence is complementary to the full-length sequence of the polynucleotide or a partial sequence thereof (referred to herein as the positive strand for convenience) based on the base pair relationship such as A: T (U), G: C. It refers to a related polynucleotide.
- complementary strand is not limited to the case where it forms a completely complementary sequence with the target positive strand base sequence, but has a complementary relationship that allows it to hybridize with the target positive strand under stringent conditions. It may be.
- stringent conditions means a nucleic acid probe that is detectable to a greater extent than other sequences (eg, average of background measurements + standard error of background measurements ⁇ measured value of 2 or more). ) And the conditions for hybridizing to the target sequence. Stringent conditions are sequence-dependent and depend on the environment in which hybridization is performed. By controlling the stringency of the hybridization and / or wash conditions, target sequences that are 100% complementary to the nucleic acid probe can be identified. Specific examples of “stringent conditions” will be described later.
- the “Tm value” means a temperature at which a double-stranded portion of a polynucleotide is denatured into a single strand and the double strand and the single strand are present at a ratio of 1: 1.
- variant refers to a natural variant caused by polymorphism, mutation, or the like, or a base sequence represented by a sequence number or a base in which u is t in the base sequence.
- a variant comprising a deletion, substitution, addition or insertion of 1, 2 or 3 or more (eg 1 to several) bases in the sequence, or a partial sequence thereof, or SEQ ID NOs: 1-210, 211-249, 250 To 374, 375 to 390, 1315 to 1350, 1351 to 1356, 1435 to 1448, and 1449 to 1453, the base sequence of the precursor RNA (premature miRNA), or u in the base sequence
- a mutant comprising a deletion, substitution, addition or insertion of one or more bases in a certain base sequence or a partial sequence thereof, or A variant showing% identity of about 90% or more, about 95% or more, about 97% or more, about 98% or more, about 99% or more with each base sequence or a partial sequence thereof, or the base sequence or
- “several” means an integer of about 10, 9, 8, 7, 6, 5, 4, 3 or 2.
- a mutant can be prepared using a well-known technique such as site-directed mutagenesis or PCR-based mutagenesis.
- % identity is based on BLAST (https://blast.ncbi.nlm.nih.gov/Blast.cgi) and FASTA (http://www.genome.jp/tools/fasta/). It can be determined using a protein or gene search system, with or without introducing a gap (Zheng Zhang et al., 2000, J. Comput. Biol., 7, p203-214; Altschul, SF, et al., 1990, Journal of Molecular Biology, Vol. 215, p403-410; Pearson, WR, et al., 1988, Proc. Natl. Acad. Sci. U.S.A., 85 , P2444-2448).
- the term “derivative” refers to a modified nucleic acid, a non-limiting group such as a labeled derivative such as a fluorophore, a modified nucleotide (for example, a halogen, an alkyl such as methyl, an alkoxy such as methoxy, a group such as thio, carboxymethyl, etc. , Derivatives including PNA (peptide nucleic acid; Nielsen, PE, etc.). 1991, Science, 254, p1497-500), LNA (locked nucleic acid; Obika, S. et al., 1998, Tetrahedron Lett., 39, p5401-5404) and the like.
- PNA peptide nucleic acid
- LNA locked nucleic acid
- a polynucleotide selected from the above-mentioned dementia marker miRNA, or a “nucleic acid” capable of specifically binding to a complementary strand of the polynucleotide is a synthesized or prepared nucleic acid, specifically Contains a “nucleic acid probe” or “primer” to detect the presence or absence of dementia in a subject, or the presence or absence of dementia, the degree of illness, the presence or absence of dementia improvement, or the degree of improvement It is used directly or indirectly for diagnosing susceptibility to treatment of dementia, or for screening candidate substances useful for prevention, amelioration or treatment of dementia.
- SEQ ID NOs: 1 to 1314 and 1315 to 1434, and 1435 to 1505 (for example, SEQ ID NOs: 194 to 212, 374, etc.) in vivo, particularly in specimens such as body fluids such as blood and urine in connection with the onset of dementia 398, 490, 591, 593-609, 766, 1015-1017, 1019-1024, 1026-1031, 1285-1286, and 1315-1434), or a cDNA synthesized nucleic acid thereof, or these Nucleotides, oligonucleotides and polynucleotides capable of specifically recognizing and binding the complementary strand of These nucleotides, oligonucleotides and polynucleotides are used as probes for detecting the gene expressed in vivo, in tissues or cells based on the above properties, and for amplifying the gene expressed in vivo. It can be effectively used as a primer.
- the term “detection” can be replaced by the term inspection, measurement, detection or decision support. Further, in this specification, the term “evaluation” is used in a meaning including supporting diagnosis or evaluation based on a test result or a measurement result.
- subject includes humans, primates including chimpanzees, pet animals such as dogs and cats, livestock animals such as cows, horses, sheep and goats, rodents such as mice and rats, Mammals such as animals raised in zoos.
- a preferred subject is a human.
- a “normal cognitive person” also means an animal that is such a mammal and does not suffer from the dementia to be detected.
- a preferred normal cognitive person is a human.
- ementia refers to a condition in which cognitive function that has once been normal has been sustainedly reduced due to an acquired brain disorder. In general, the diagnosis is made when there is a decrease in function to the extent that it interferes with daily life and social life.
- Dementia is generally classified into disease types such as Alzheimer type dementia, vascular dementia, Lewy body dementia, normal pressure hydrocephalus, frontotemporal lobar degeneration, etc., depending on the causative disease.
- “dementia” includes Alzheimer-type dementia, vascular dementia, Lewy body dementia, normal pressure hydrocephalus, frontotemporal lobar degeneration, neurofibrillary tangle dementia, other Dementia such as dementia, alcoholic dementia, vitamin deficiency dementia caused by disease (infection etc.) is included.
- “dementia” in the present invention includes dementia that is a mixed type of any of these disease types.
- dementia whose disease type is unknown or unspecified is also included in the “dementia” in the present invention.
- Alzheimer's-type dementia is a core symptom of cognitive memory impairment due to atrophy of the medial temporal lobe without abnormal brain structures in CT, MRI, and PET imaging tests. Is a dementia with approximate memory impairment.
- vascular dementia appears in connection with cerebrovascular disorders, and cognitive memory disorders are heterogeneous or patchy and have a decline in memory and intellectual ability. Dementia that is relatively well maintained.
- Lewy body dementia refers to a decrease in dopamine transporter uptake in the basal ganglia by cerebral blood flow SPECT or PET imaging. This is a dementia with parkinsonism, hallucinations that repeatedly appear.
- normal pressure hydrocephalus is a dementia in which cerebrospinal fluid accumulates in the ventricle and compresses the surrounding brain, resulting in cognitive impairment, gait disturbance, and dysuria. Dementia that can be improved by surgical treatment.
- frontotemporal lobar degeneration is a dementia that exhibits language impairment and psychiatric symptoms due to significant atrophy of the frontal and temporal lobes.
- P or “P value” refers to the probability that, in a statistical test, a statistic more extreme than the statistic actually calculated from the data under the null hypothesis is observed. Indicates. Therefore, it can be considered that the smaller the “P” or “P value”, the more significant the difference between the comparison objects.
- sensitivity means a value of (number of true positives) / (number of true positives + number of false negatives). If the sensitivity is high, dementia can be detected early, and early medical intervention is possible.
- specificity means (number of true negatives) / (number of true negatives + number of false positives). If the specificity is high, it is possible to prevent a person with normal cognitive function from being misidentified as a patient with dementia and to carry out a wasteful additional test, thereby reducing the burden on the patient and medical costs.
- accuracy means a value of (number of true positives + number of true negatives) / (number of all cases). The accuracy indicates the rate at which the discrimination results for all the samples are correct, and is a first index for evaluating the detection performance.
- the “specimen” to be determined, detected or diagnosed is a tissue or living body in which the gene of the present invention changes in expression as a result of the occurrence of dementia, the progression of dementia, and the exertion of a therapeutic effect on dementia.
- material Specifically, brain tissue and nerve cells, nerve tissue, cerebrospinal fluid, bone marrow fluid, organs, skin, and body fluids such as blood, urine, saliva, sweat, tissue exudate, serum prepared from blood, plasma, etc.
- the biological sample extracted from these specifically refers to genes such as RNA and miRNA.
- hsa-miR-4274 gene or “hsa-miR-4274” refers to the hsa-miR-4274 gene (miRBase Accession No. MIMAT0016906) described in SEQ ID NO: 1 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4274 gene was obtained from Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192.
- hsa-miR-4274 “hsa-mir-4274” (miRBase Accession No. MI0015884, SEQ ID NO: 391), which has a hairpin-like structure as a precursor, is known.
- hsa-miR-4272 gene or “hsa-miR-4272” refers to the hsa-miR-4272 gene (miRBase Accession No. MIMAT0016902) described in SEQ ID NO: 2 and other biological species. Homologs or orthologs are included. The hsa-miR-4272 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-4272”, “hsa-mir-4272” (miRBase Accession No. MI0015880, SEQ ID NO: 392) having a hairpin-like structure as a precursor is known.
- hsa-miR-4728-5p gene or “hsa-miR-4728-5p” refers to the hsa-miR-4728-5p gene described in SEQ ID NO: 3 (miRBase Accession No. MIMAT0019849) and other species homologues or orthologues are included.
- the hsa-miR-4728-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4728-5p “hsa-mir-4728” (miRBase Accession No. MI0017365, SEQ ID NO: 393) having a hairpin-like structure as a precursor is known.
- hsa-miR-4443 gene or “hsa-miR-4443” refers to the hsa-miR-4443 gene (miRBase Accession No. MIMAT0018961) described in SEQ ID NO: 4 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4443 gene is described in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-miR-4443 is known as “hsa-mir-4443” (miRBase Accession No. MI0016786, SEQ ID NO: 394) having a hairpin-like structure as a precursor.
- hsa-miR-4506 gene or “hsa-miR-4506” refers to the hsa-miR-4506 gene (miRBase Accession No. MIMAT0019042) described in SEQ ID NO: 5 and other biological species. Homologs or orthologs are included.
- the hsa-miR-4506 gene can be found in Jim DD et al., 2010, Blood. 116, e118-e127.
- “Hsa-miR-4506” is known as “hsa-mir-4506” (miRBase Accession No. MI0016869, SEQ ID NO: 395), which has a hairpin-like structure as a precursor.
- hsa-miR-6773-5p gene or “hsa-miR-6773-5p” refers to the hsa-miR-6773-5p gene described in SEQ ID NO: 6 (miRBase Accession No. MIMAT0027446) and other species homologues or orthologues are included.
- the hsa-miR-6773-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6773-5p “hsa-mir-6773” (miRBase Accession No. MI0022618, SEQ ID NO: 396) having a hairpin-like structure as a precursor is known.
- hsa-miR-4662a-5p gene or “hsa-miR-4662a-5p” refers to the hsa-miR-4662a-5p gene described in SEQ ID NO: 7 (miRBase Accession No. MIMAT0019731) and other species homologues or orthologues are included.
- the hsa-miR-4662a-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4661a-5p “hsa-mir-4662a” (miRBase Accession No. MI0017290, SEQ ID NO: 397) having a hairpin-like structure as a precursor is known.
- hsa-miR-3184-3p gene or “hsa-miR-3184-3p” refers to the hsa-miR-3184-3p gene described in SEQ ID NO: 8 (miRBase Accession No. MIMAT0022731) and other species homologues or orthologues are included.
- the hsa-miR-3184-3p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “hsa-miR-3184-3p” is known as “hsa-mir-3184” (miRBase Accession No. MI0014226, SEQ ID NO: 398) having a hairpin-like structure as a precursor.
- hsa-miR-4281 gene or “hsa-miR-4281” refers to the hsa-miR-4281 gene (miRBase Accession No. MIMAT0016907) described in SEQ ID NO: 9 or other biological species. Homologs or orthologs are included. The hsa-miR-4281 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-4281”, “hsa-mir-4281” (miRBase Accession No. MI0015885, SEQ ID NO: 399) having a hairpin-like structure as a precursor is known.
- hsa-miR-320d gene or “hsa-miR-320d” refers to the hsa-miR-320d gene (miRBase Accession No. MIMAT0006764) described in SEQ ID NO: 10 or other biological species. Homologs or orthologs are included.
- the hsa-miR-320d gene is described in Friedlander MR et al., 2008, Nat Biotechnol. 26, 407-415.
- “hsa-miR-320d” has a hairpin-like structure as its precursor, “hsa-mir-320d-1, hsa-mir-320d-2” (miRBase Accession No. MI0008190, MI0008192, SEQ ID NO: 400, 401) is known.
- hsa-miR-6729-3p gene or “hsa-miR-6729-3p” refers to the hsa-miR-6729-3p gene described in SEQ ID NO: 11 (miRBase Accession No. MIMAT0027360) and other species homologs or orthologs.
- the hsa-miR-6729-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6729-3p “hsa-mir-6729” (miRBase Accession No. MI0022574, SEQ ID NO: 402) having a hairpin-like structure as a precursor is known.
- hsa-miR-5192 gene or “hsa-miR-5192” refers to the hsa-miR-5192 gene (miRBase Accession No. MIMAT0021123) described in SEQ ID NO: 12 and other biological species. Homologs or orthologs are included.
- the hsa-miR-5192 gene was obtained from Schotte et al., 2011, Leukemia. 25, 1389-1399.
- hsa-miR-5192 “hsa-mir-5192” (miRBase Accession No. MI0018171, SEQ ID NO: 403) having a hairpin-like structure as a precursor is known.
- hsa-miR-6683-5p gene or “hsa-miR-6833-5p” refers to the hsa-miR-6683-5p gene (miRBase Accession No. 6) described in SEQ ID NO: 13. MIMAT0027606) and other species homologues or orthologues are included.
- the hsa-miR-6683-5p gene was obtained from Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6833-5p” is known as “hsa-mir-6853” (miRBase Accession No. MI0022699, SEQ ID NO: 404) having a hairpin-like structure as a precursor.
- hsa-miR-1234-3p gene or “hsa-miR-1234-3p” refers to the hsa-miR-1234-3p gene described in SEQ ID NO: 14 (miRBase Accession No. MIMAT0005589) and other species homologues or orthologues are included.
- the hsa-miR-1234-3p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- hsa-mir-1234 (miRBase Accession No. MI0006324, SEQ ID NO: 405) having a hairpin-like structure as a precursor is known.
- hsa-miR-1233-3p gene or “hsa-miR-1233-3p” refers to the hsa-miR-1233-3p gene described in SEQ ID NO: 15 (miRBase Accession No. MIMAT0005588) and other species homologues or orthologues are included.
- the hsa-miR-1233-3p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- “hsa-miR-1233-3p” has “hsa-mir-1233-1, hsa-mir-12233-2” (miRBase Accession No. MI0006323, MI0015973, SEQ ID NO :) having a hairpin-like structure as a precursor. 406, 407) are known.
- hsa-miR-4539 gene or “hsa-miR-4539” refers to the hsa-miR-4539 gene (miRBase Accession No. MIMAT0019082) described in SEQ ID NO: 16 and other biological species. Homologs or orthologs are included.
- the hsa-miR-4539 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4539 (miRBase Accession No. MI0016910, SEQ ID NO: 408) having a hairpin-like structure as a precursor is known.
- hsa-miR-3914 gene or “hsa-miR-3914” refers to the hsa-miR-3914 gene (miRBase Accession No. MIMAT0018188) described in SEQ ID NO: 17 and other biological species. Homologs or orthologs are included. The hsa-miR-3914 gene was found in Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- “Hsa-miR-3914” has a hairpin-like structure as a precursor thereof, “hsa-mir-3914-1, hsa-mir-3914-2” (miRBase Accession No. MI0016419, MI0016421, SEQ ID NO: 409, 410) is known.
- hsa-miR-4738-5p gene or “hsa-miR-4738-5p” refers to the hsa-miR-4738-5p gene described in SEQ ID NO: 18 (miRBase Accession No. MIMAT0019866) and other species homologs or orthologs.
- the hsa-miR-4738-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4738-5p “hsa-mir-4738” (miRBase Accession No. MI0017376, SEQ ID NO: 411) having a hairpin-like structure as a precursor is known.
- hsa-miR-548au-3p gene or “hsa-miR-548au-3p” refers to the hsa-miR-548au-3p gene described in SEQ ID NO: 19 (miRBase Accession No. 1). MIMAT0022292) and other species homologues or orthologues are included.
- the hsa-miR-548au-3p gene was found in Friedlander MR et al., 2012, Nucleic Acids Res. 40, 37-52.
- “hsa-miR-548au-3p” is known as “hsa-mir-548au” (miRBase Accession No. MI0019145, SEQ ID NO: 412) having a hairpin-like structure as a precursor.
- hsa-miR-1539 gene or “hsa-miR-1539” refers to the hsa-miR-1539 gene (miRBase Accession No. MIMAT0007401) described in SEQ ID NO: 20 and other biological species. Homologs or orthologs are included.
- the hsa-miR-1539 gene was obtained from Azuma-Mukai A et al., 2008, Proc Natl Acad Sci US A. 105, 7964-7969.
- hsa-miR-1539 is known as “hsa-mir-1539” (miRBase Accession No. MI0007260, SEQ ID NO: 413) having a hairpin-like structure as a precursor.
- hsa-miR-4720-3p gene or “hsa-miR-4720-3p” refers to the hsa-miR-4720-3p gene described in SEQ ID NO: 21 (miRBase Accession No. MIMAT0019834) and other species homologues or orthologues are included.
- the hsa-miR-4720-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4720-3p” is known as “hsa-mir-4720” (miRBase Accession No. MI0017355, SEQ ID NO: 414) having a hairpin-like structure as a precursor.
- hsa-miR-365b-5p gene or “hsa-miR-365b-5p” refers to the hsa-miR-365b-5p gene described in SEQ ID NO: 22 (miRBase Accession No. MIMAT0022833) and other species homologs or orthologs.
- the hsa-miR-365b-5p gene is described in Xie X et al., 2005, Nature. 434, 338-345.
- hsa-miR-365b-5p “hsa-mir-365b” (miRBase Accession No. MI000069, SEQ ID NO: 415) having a hairpin-like structure as a precursor is known.
- hsa-miR-4486 gene or “hsa-miR-4486” refers to the hsa-miR-4486 gene (miRBase Accession No. MIMAT0019020) described in SEQ ID NO: 23 and other biological species. Homologs or orthologs are included. The hsa-miR-4486 gene was found in Jim DD et al., 2010, Blood. 116, e118-e127. As for “hsa-miR-4486”, “hsa-mir-4486” (miRBase Accession No. MI0016847, SEQ ID NO: 416) having a hairpin-like structure as a precursor is known.
- hsa-miR-1227-5p gene or “hsa-miR-1227-5p” refers to the hsa-miR-1227-5p gene described in SEQ ID NO: 24 (miRBase Accession No. MIMAT0022941) and other species homologues or orthologues are included.
- the hsa-miR-1227-5p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- “hsa-miR-1227-5p” is known as “hsa-mir-1227” (miRBase Accession No. MI0006316, SEQ ID NO: 417) having a hairpin-like structure as a precursor.
- hsa-miR-4667-5p gene or “hsa-miR-4667-5p” refers to the hsa-miR-4667-5p gene described in SEQ ID NO: 25 (miRBase Accession No. MIMAT0019743) and other species homologues or orthologues are included.
- the hsa-miR-4667-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4667-5p “hsa-mir-4667” (miRBase Accession No. MI0017297, SEQ ID NO: 418) having a hairpin-like structure as a precursor is known.
- hsa-miR-6088 gene or “hsa-miR-6088” refers to the hsa-miR-6088 gene (miRBase Accession No. MIMAT0023713) described in SEQ ID NO: 26 and other biological species. Homologs or orthologs are included.
- the hsa-miR-6088 gene was obtained from Yoo JK et al., 2012, Stem Cells Dev. 21, 2049-2057.
- hsa-miR-6088 “hsa-mir-6088” (miRBase Accession No. MI0020365, SEQ ID NO: 419) having a hairpin-like structure as a precursor is known.
- hsa-miR-6820-5p gene or “hsa-miR-6820-5p” refers to the hsa-miR-6820-5p gene described in SEQ ID NO: 27 (miRBase Accession No. MIMAT0027540) and other species homologs or orthologs.
- the hsa-miR-6820-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6820-5p” is known as “hsa-mir-6820” (miRBase Accession No. MI0022665, SEQ ID NO: 420) having a hairpin-like structure as a precursor.
- hsa-miR-4505 gene or “hsa-miR-4505” refers to the hsa-miR-4505 gene (miRBase Accession No. MIMAT0019041) described in SEQ ID NO: 28 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4505 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- “Hsa-miR-4505” is known as “hsa-mir-4505” (miRBase Accession No. MI0016868, SEQ ID NO: 421) having a hairpin-like structure as a precursor.
- hsa-miR-548q gene or “hsa-miR-548q” refers to the hsa-miR-548q gene (miRBase Accession No. MIMAT0011163) described in SEQ ID NO: 29 or other biological species. Homologs or orthologs are included.
- the hsa-miR-548q gene was obtained from Wyman SK et al., 2009, PLoS One. 4, Volume 4, e5311.
- hsa-miR-548q “hsa-mir-548q” (miRBase Accession No. MI0010637, SEQ ID NO: 422) having a hairpin-like structure as a precursor is known.
- hsa-miR-4658 gene or “hsa-miR-4658” refers to the hsa-miR-4658 gene (miRBase Accession No. MIMAT0019725) described in SEQ ID NO: 30 and other biological species. Homologs or orthologs are included.
- the hsa-miR-4658 gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4658 “hsa-mir-4658” (miRBase Accession No. MI0017286, SEQ ID NO: 423) having a hairpin-like structure as a precursor is known.
- hsa-miR-450a-5p gene or “hsa-miR-450a-5p” refers to the hsa-miR-450a-5p gene described in SEQ ID NO: 31 (miRBase Accession No. MIMAT001545) and other species homologs or orthologs.
- the hsa-miR-450a-5p gene is described in Xie X et al., 2005, Nature. 434, 338-345.
- “Hsa-miR-450a-5p” has a hairpin-like structure as its precursor, “hsa-mir-450a-1, hsa-mir-450a-2” (miRBase Accession No. MI0001652, MI0003187, SEQ ID NO: 424, 425) is known.
- hsa-miR-1260b gene or “hsa-miR-1260b” refers to the hsa-miR-1260b gene (miRBase Accession No. MIMAT0015041) described in SEQ ID NO: 32 and other biological species. Homologs or orthologs are included.
- the hsa-miR-1260b gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- hsa-miR-1260b “hsa-mir-1260b” (miRBase Accession No. MI0014197, SEQ ID NO: 426) having a hairpin-like structure as a precursor is known.
- hsa-miR-3777-5p gene or “hsa-miR-3777-5p” refers to the hsa-miR-3777-5p gene described in SEQ ID NO: 33 (miRBase Accession No. MIMAT0019221) and other species homologues or orthologues are included.
- the hsa-miR-3777-5p gene was obtained from Vaz C et al., 2010, BMC Genomics. 11 and 288.
- hsa-miR-3777-5p “hsa-mir-3677” (miRBase Accession No. MI0016078, SEQ ID NO: 427) having a hairpin-like structure as a precursor is known.
- hsa-miR-6777-3p gene or “hsa-miR-6777-3p” refers to the hsa-miR-6777-3p gene described in SEQ ID NO: 34 (miRBase Accession No. MIMAT0027455) and other species homologs or orthologs.
- the hsa-miR-6777-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6777-3p” is known as “hsa-mir-6777” (miRBase Accession No. MI0022622, SEQ ID NO: 428) having a hairpin-like structure as a precursor.
- hsa-miR-6826-3p gene or “hsa-miR-6826-3p” refers to the hsa-miR-6826-3p gene described in SEQ ID NO: 35 (miRBase Accession No. MIMAT0027553) and other species homologs or orthologs.
- the hsa-miR-6826-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6826-3p” is known as “hsa-mir-6826” (miRBase Accession No. MI0022671, SEQ ID NO: 429) having a hairpin-like structure as a precursor.
- hsa-miR-6832-p gene or “hsa-miR-6832-p” refer to the hsa-miR-6832-p gene (miRBase Accession No. 36) described in SEQ ID NO: 36. MIMAT0027565) and other species homologs or orthologs.
- the hsa-miR-6832-p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “Hsa-miR-6832-p” is known as “hsa-mir-6632” (miRBase Accession No. MI0022677, SEQ ID NO: 430) having a hairpin-like structure as a precursor.
- hsa-miR-4725-3p gene or “hsa-miR-4725-3p” refers to the hsa-miR-4725-3p gene described in SEQ ID NO: 37 (miRBase Accession No. MIMAT0019844) and other species homologs or orthologs.
- the hsa-miR-4725-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4725-3p “hsa-mir-4725” (miRBase Accession No. MI0017362, SEQ ID NO: 431) having a hairpin-like structure as a precursor is known.
- hsa-miR-7161-3p gene or “hsa-miR-7161-3p” refers to the hsa-miR-7161-3p gene described in SEQ ID NO: 38 (miRBase Accession No. MIMAT0028233) and other species homologs or orthologs.
- the hsa-miR-7161-3p gene is described in Meunier J et al., 2013, Genome Res. 23, 34-45.
- “hsa-miR-7161-3p” is known as “hsa-mir-7161” (miRBase Accession No. MI0023619, SEQ ID NO: 432) having a hairpin-like structure as a precursor.
- hsa-miR-2277-5p gene or “hsa-miR-2277-5p” refers to the hsa-miR-2277-5p gene (miRBase Accession No. MIMAT0017352) and other species homologues or orthologues are included.
- the hsa-miR-2277-5p gene was obtained from Nygaard S et al., 2009, BMC Med Genomics. 2 and 35.
- “hsa-miR-2277-5p” is known as “hsa-mir-2277” (miRBase Accession No. MI0011284, SEQ ID NO: 433) having a hairpin-like structure as a precursor.
- hsa-miR-7110-3p gene or “hsa-miR-7110-3p” refers to the hsa-miR-7110-3p gene described in SEQ ID NO: 40 (miRBase Accession No. MIMAT0028118) and other species homologs or orthologs are included.
- the hsa-miR-7110-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-7110-3p” is known as “hsa-mir-7110” (miRBase Accession No. MI0022961, SEQ ID NO: 434) having a hairpin-like structure as a precursor.
- hsa-miR-4312 gene or “hsa-miR-4312” refers to the hsa-miR-4312 gene (miRBase Accession No. MIMAT0016864) described in SEQ ID NO: 41 or other species. Homologs or orthologs are included. The hsa-miR-4312 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-4312”, “hsa-mir-4312” (miRBase Accession No. MI0015842, SEQ ID NO: 435) having a hairpin-like structure as a precursor is known.
- hsa-miR-4461 gene or “hsa-miR-4461” refers to the hsa-miR-4461 gene (miRBase Accession No. MIMAT0018983) described in SEQ ID NO: 42 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4461 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4461 (miRBase Accession No. MI0016807, SEQ ID NO: 436) having a hairpin-like structure as a precursor is known.
- hsa-miR-6766-5p gene or “hsa-miR-6766-5p” refers to the hsa-miR-6766-5p gene described in SEQ ID NO: 43 (miRBase Accession No. MIMAT0027432) and other species homologues or orthologues are included.
- the hsa-miR-6766-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6766-5p” is known as “hsa-mir-6766” (miRBase Accession No. MI0022611, SEQ ID NO: 437) having a hairpin-like structure as a precursor.
- hsa-miR-1266-3p gene or “hsa-miR-1266-3p” refers to the hsa-miR-1266-3p gene described in SEQ ID NO: 44 (miRBase Accession No. MIMAT0026742) and other species homologues or orthologues are included.
- the hsa-miR-1266-3p gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- “Hsa-miR-1266-3p” is known as “hsa-mir-1266” (miRBase Accession No. MI0006403, SEQ ID NO: 438) having a hairpin-like structure as a precursor.
- hsa-miR-6729-5p gene or “hsa-miR-6729-5p” refers to the hsa-miR-6729-5p gene described in SEQ ID NO: 45 (miRBase Accession No. MIMAT0027359) and other species homologues or orthologues are included.
- the hsa-miR-6729-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6729-5p” is known as “hsa-mir-6729” (miRBase Accession No. MI0022574, SEQ ID NO: 402) having a hairpin-like structure as a precursor.
- hsa-miR-526b-3p gene or “hsa-miR-526b-3p” refers to the hsa-miR-526b-3p gene described in SEQ ID NO: 46 (miRBase Accession No. MIMAT0002836) and other species homologues or orthologues are included.
- the hsa-miR-526b-3p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-526b-3p “hsa-mir-526b” (miRBase Accession No. MI0003150, SEQ ID NO: 439) having a hairpin-like structure as a precursor is known.
- hsa-miR-519e-5p gene or “hsa-miR-519e-5p” refers to the hsa-miR-519e-5p gene described in SEQ ID NO: 47 (miRBase Accession No. MIMAT0002828) and other species homologs or orthologs.
- the hsa-miR-519e-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-519e-5p “hsa-mir-519e” (miRBase Accession No. MI0003145, SEQ ID NO: 440) having a hairpin-like structure as a precursor is known.
- hsa-miR-512-5p gene or “hsa-miR-512-5p” refers to the hsa-miR-512-5p gene described in SEQ ID NO: 48 (miRBase Accession No. MIMAT0002822) and other species homologs or orthologs are included.
- the hsa-miR-512-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-512-5p” has “hsa-mir-512-1, hsa-mir-512-2” (miRBase Accession No. MI0003140, MI0003141, SEQ ID NO. 441, 442) are known.
- hsa-miR-5088-5p gene or “hsa-miR-5088-5p” refers to the hsa-miR-5088-5p gene described in SEQ ID NO: 49 (miRBase Accession No. MIMAT0021080) and other species homologs or orthologs.
- the hsa-miR-5088-5p gene is disclosed in Ding N et al., 2011, J Radiat Res. 52, 425-432.
- “hsa-miR-5088-5p” is known as “hsa-mir-5088” (miRBase Accession No. MI0017977, SEQ ID NO: 443) having a hairpin-like structure as a precursor.
- hsa-miR-1909-3p gene or “hsa-miR-1909-3p” refers to the hsa-miR-1909-3p gene described in SEQ ID NO: 50 (miRBase Accession No. MIMAT0007883) and other species homologs or orthologs.
- the hsa-miR-1909-3p gene is described in Bar M et al., 2008, Stem Cells. 26, 2496-2505.
- “Hsa-miR-1909-3p” is known as “hsa-mir-1909” (miRBase Accession No. MI0008330, SEQ ID NO: 444) having a hairpin-like structure as a precursor.
- hsa-miR-6511a-5p gene or “hsa-miR-6511a-5p” refers to the hsa-miR-6511a-5p gene described in SEQ ID NO: 51 (miRBase Accession No. MIMAT0025478) and other species homologues or orthologues are included.
- the hsa-miR-6511a-5p gene was obtained from Joyce CE et al., 2011, Hum Mol Genet. 20, Vol. 4025-4040.
- hsa-miR-6511a-5p has a hairpin-like structure as its precursor, “hsa-mir-6651a-1, hsa-mir-6511a-2, hsa-mir-6651a-3, hsa-mir”.
- -6511a-4 "(miRBBase Accession No. MI0022223, MI0023564, MI0023565, MI0023566, SEQ ID NOs: 445, 446, 447, 448) are known.
- hsa-miR-4734 gene or “hsa-miR-4734” refers to the hsa-miR-4734 gene (miRBase Accession No. MIMAT0019859) described in SEQ ID NO: 52 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4734 gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4734 “hsa-mir-4734” (miRBase Accession No. MI0017371, SEQ ID NO: 449) having a hairpin-like structure as a precursor is known.
- hsa-miR-936 gene or “hsa-miR-936” refers to the hsa-miR-936 gene (miRBase Accession No. MIMAT0004979) described in SEQ ID NO: 53 and other biological species. Homologs or orthologs are included.
- the hsa-miR-936 gene is disclosed in Lui WO et al., 2007, Cancer Res. 67, 6031-6043.
- hsa-miR-936 “hsa-mir-936” (miRBase Accession No. MI0005758, SEQ ID NO: 450) having a hairpin-like structure as a precursor is known.
- hsa-miR-1249-3p gene or “hsa-miR-1249-3p” refers to the hsa-miR-1249-3p gene described in SEQ ID NO: 54 (miRBase Accession No. MIMAT0005901) and other species homologues or orthologues are included.
- the hsa-miR-1249-3p gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- hsa-miR-1249-3p “hsa-mir-1249” (miRBase Accession No. MI0006384, SEQ ID NO: 451) having a hairpin-like structure as a precursor is known.
- hsa-miR-6777-5p gene or “hsa-miR-6777-5p” refers to the hsa-miR-6777-5p gene described in SEQ ID NO: 55 (miRBase Accession No. MIMAT0027454) and other species homologues or orthologues are included.
- the hsa-miR-6777-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6777-5p “hsa-mir-6777” (miRBase Accession No. MI0022622, SEQ ID NO: 428) having a hairpin-like structure as a precursor is known.
- hsa-miR-4487 gene or “hsa-miR-4487” refers to the hsa-miR-4487 gene (miRBase Accession No. MIMAT0019021) described in SEQ ID NO: 56 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4487 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-miR-4487 is known as “hsa-mir-4487” (miRBase Accession No. MI0016848, SEQ ID NO: 452) having a hairpin-like structure as a precursor.
- hsa-miR-3155a gene or “hsa-miR-3155a” refers to the hsa-miR-3155a gene (miRBase Accession No. MIMAT0015029) described in SEQ ID NO: 57 and other biological species. Homologs or orthologs are included. The hsa-miR-3155a gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685. As for “hsa-miR-3155a”, “hsa-mir-3155a” (miRBase Accession No. MI0014183, SEQ ID NO: 453) having a hairpin-like structure as a precursor is known.
- hsa-miR-563 gene or “hsa-miR-563” refers to the hsa-miR-563 gene (miRBase Accession No. MIMAT0003227) described in SEQ ID NO: 58 or other biological species. Homologs or orthologs are included.
- the hsa-miR-563 gene was obtained from Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- “Hsa-miR-563” is known as “hsa-mir-563” (miRBase Accession No. MI0003569, SEQ ID NO: 454) having a hairpin-like structure as a precursor.
- hsa-miR-4741 gene or “hsa-miR-4741” refers to the hsa-miR-4741 gene (miRBase Accession No. MIMAT0019871) described in SEQ ID NO: 59 and other biological species. Homologs or orthologs are included.
- the hsa-miR-4741 gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4741 “hsa-mir-4741” (miRBase Accession No. MI0017379, SEQ ID NO: 455) having a hairpin-like structure as a precursor is known.
- hsa-miR-6788-5p gene or “hsa-miR-6788-5p” refers to the hsa-miR-6788-5p gene described in SEQ ID NO: 60 (miRBase Accession No. MIMAT0027476) and other species homologs or orthologs.
- the hsa-miR-6788-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6788-5p” is known as “hsa-mir-6788” (miRBase Accession No. MI0022633, SEQ ID NO: 456) having a hairpin-like structure as a precursor.
- hsa-miR-4433b-5p gene or “hsa-miR-4433b-5p” refers to the hsa-miR-4433b-5p gene described in SEQ ID NO: 61 (miRBase Accession No. MIMAT0030413) and other species homologues or orthologues are included.
- the hsa-miR-4433b-5p gene was found in Ple H et al., 2012, PLoS One. 7, Vol. 7, e50746.
- hsa-miR-4433b-5p “hsa-mir-4433b” (miRBase Accession No. MI0025511, SEQ ID NO: 457) having a hairpin-like structure as a precursor is known.
- hsa-miR-323a-5p gene or “hsa-miR-323a-5p” refers to the hsa-miR-323a-5p gene described in SEQ ID NO: 62 (miRBase Accession No. MIMAT0004696) and other species homologs or orthologs.
- the hsa-miR-323a-5p gene was found in Kim J et al., 2004, Proc Natl Acad Sci USA. 101, 360-365.
- “hsa-miR-323a-5p” “hsa-mir-323a” (miRBase Accession No. MI0000807, SEQ ID NO: 458) having a hairpin-like structure as a precursor is known.
- hsa-miR-6811-5p gene or “hsa-miR-6811-5p” refers to the hsa-miR-6811-5p gene described in SEQ ID NO: 63 (miRBase Accession No. MIMAT0027522) and other species homologs or orthologs.
- the hsa-miR-6811-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6811-5p “hsa-mir-6811” (miRBase Accession No. MI0022656, SEQ ID NO: 459) having a hairpin-like structure as a precursor is known.
- hsa-miR-6721-5p gene or “hsa-miR-6721-5p” refers to the hsa-miR-6721-5p gene described in SEQ ID NO: 64 (miRBase Accession No. MIMAT0025852) and other species homologs or orthologs.
- the hsa-miR-6721-5p gene is disclosed in Li Y et al., 2012, Gene. 497, 330-335.
- hsa-miR-6721-5p “hsa-mir-6721” (miRBase Accession No. MI0022556, SEQ ID NO: 460) having a hairpin-like structure as a precursor is known.
- hsa-miR-5004-5p gene or “hsa-miR-5004-5p” refers to the hsa-miR-5004-5p gene described in SEQ ID NO: 65 (miRBase Accession No. MIMAT0021027) and other species homologs or orthologs.
- the hsa-miR-5004-5p gene was obtained from Hansen TB et al., 2011, RNA Biol. 8, 378-383.
- hsa-miR-5004-5p “hsa-mir-5004” (miRBase Accession No. MI0017870, SEQ ID NO: 461) having a hairpin-like structure as a precursor is known.
- hsa-miR-6509-3p gene or “hsa-miR-6509-3p” refers to the hsa-miR-6509-3p gene described in SEQ ID NO: 66 (miRBase Accession No. MIMAT0025475) and other species homologues or orthologues are included.
- the hsa-miR-6509-3p gene was obtained from Joyce CE et al., 2011, Hum Mol Genet. 20, Vol. 4025-4040.
- “hsa-miR-6509-3p” is known as “hsa-mir-6509” (miRBase Accession No. MI0022221, SEQ ID NO: 462) having a hairpin-like structure as a precursor.
- hsa-miR-648 gene or “hsa-miR-648” refers to the hsa-miR-648 gene (miRBase Accession No. MIMAT0003318) described in SEQ ID NO: 67 and other biological species. Homologs or orthologs are included. The hsa-miR-648 gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692. As for “hsa-miR-648”, “hsa-mir-648” (miRBase Accession No. MI0003663, SEQ ID NO: 463) having a hairpin-like structure as a precursor is known.
- hsa-miR-3717 gene or “hsa-miR-3913” refers to the hsa-miR-3717 gene (miRBase Accession No. MIMAT0018191) described in SEQ ID NO: 68 and other biological species. Homologs or orthologs are included.
- the hsa-miR-3918 gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- hsa-miR-3917 is known as “hsa-mir-3917” (miRBase Accession No. MI0016423, SEQ ID NO: 464) having a hairpin-like structure as a precursor.
- hsa-miR-6087 gene or “hsa-miR-6087” refers to the hsa-miR-6087 gene (miRBase Accession No. MIMAT0023712) described in SEQ ID NO: 69 or other species. Homologs or orthologs are included.
- the hsa-miR-6087 gene was obtained from Yoo JK et al., 2012, Stem Cells Dev. 21, 2049-2057.
- hsa-miR-6087 “hsa-mir-6087” (miRBase Accession No. MI0020364, SEQ ID NO: 465) having a hairpin-like structure as a precursor is known.
- hsa-miR-1470 gene or “hsa-miR-1470” refers to the hsa-miR-1470 gene (miRBase Accession No. MIMAT0007348) described in SEQ ID NO: 70 or other biological species. Homologs or orthologs are included. The hsa-miR-1470 gene was found in Kawaji H et al., 2008, BMC Genomics. , Vol. 9, 157. Also, “hsa-miR-1470” is known as “hsa-mir-1470” (miRBase Accession No. MI00000075, SEQ ID NO: 466) having a hairpin-like structure as a precursor.
- hsa-miR-586 gene or “hsa-miR-586” refers to the hsa-miR-586 gene (miRBase Accession No. MIMAT0003252) described in SEQ ID NO: 71 or other biological species. A homolog or ortholog is included.
- the hsa-miR-586 gene was obtained from Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- hsa-miR-586 “hsa-mir-586” (miRBase Accession No. MI0003594, SEQ ID NO: 467) having a hairpin-like structure as a precursor is known.
- hsa-miR-3150a-5p gene or “hsa-miR-3150a-5p” refers to the hsa-miR-3150a-5p gene described in SEQ ID NO: 72 (miRBase Accession No. MIMAT0019206) and other species homologs or orthologs.
- the hsa-miR-3150a-5p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “Hsa-miR-3150a-5p” is known as “hsa-mir-3150a” (miRBase Accession No. MI0014177, SEQ ID NO: 468) having a hairpin-like structure as a precursor.
- hsa-miR-105-3p gene or “hsa-miR-105-3p” refers to the hsa-miR-105-3p gene described in SEQ ID NO: 73 (miRBase Accession No. MIMAT0004516) and other species homologues or orthologues are included.
- the hsa-miR-105-3p gene is described in Mouretos Z et al., 2002, Genes Dev. 16, 720-728.
- “hsa-miR-105-3p” has “hsa-mir-105-1, hsa-mir-105-2” (miRBBase Accession No. MI0000111, MI0000112, SEQ ID NO. 469, 470).
- hsa-miR-7773 gene or “hsa-miR-7793” refers to the hsa-miR-7793 gene (miRBase Accession No. MIMAT0031176) described in SEQ ID NO: 74 or other biological species. Homologs or orthologs are included.
- the hsa-miR-797 gene was obtained from Velthut-Meikas A, et al., 2013, Endocrinol. 27, 1128-1141.
- hsa-miR-7793 has a hairpin-like structure as a precursor thereof, “hsa-mir-7793-1, hsa-mir-7793-2” (miRBase Accession No. MI0025748, MI0025749, SEQ ID NO: 471, 472) is known.
- hsa-miR-1914-5p gene or “hsa-miR-1914-5p” refers to the hsa-miR-1914-5p gene (miRBase Accession No. MIMAT0007889) and other species homologs or orthologs.
- the hsa-miR-1914-5p gene is described in Bar M et al., 2008, Stem Cells. 26, 2496-2505.
- “hsa-miR-1914-5p” is known as “hsa-mir-1914” (miRBase Accession No. MI0008335, SEQ ID NO: 473) having a hairpin-like structure as a precursor.
- hsa-miR-4749-3p gene or “hsa-miR-4749-3p” refers to the hsa-miR-4749-3p gene described in SEQ ID NO: 76 (miRBase Accession No. MIMAT0019886) and other species homologues or orthologues are included.
- the hsa-miR-4749-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4749-3p” is known as “hsa-mir-4749” (miRBase Accession No. MI0017388, SEQ ID NO: 474) having a hairpin-like structure as a precursor.
- hsa-miR-15b-5p gene or “hsa-miR-15b-5p” refers to the hsa-miR-15b-5p gene described in SEQ ID NO: 77 (miRBase Accession No. MIMAT000017) and other species homologues or orthologues are included.
- the hsa-miR-15b-5p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- “hsa-miR-15b-5p” is known as “hsa-mir-15b” (miRBase Accession No. MI0000438, SEQ ID NO: 475) having a hairpin-like structure as a precursor.
- hsa-miR-1289 gene or “hsa-miR-1289” refers to the hsa-miR-1289 gene (miRBase Accession No. MIMAT0005879) described in SEQ ID NO: 78 and other biological species. Homologs or orthologs are included.
- the hsa-miR-1289 gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- “hsa-miR-1289” has “hsa-mir-1289-1, hsa-mir-1289-2” (miRBase Accession No. MI0006350, MI0006351, SEQ ID NO: 476, taking a hairpin-like structure as a precursor 477) is known.
- hsa-miR-4433a-5p gene or “hsa-miR-4433a-5p” refers to the hsa-miR-4433a-5p gene described in SEQ ID NO: 79 (miRBase Accession No. MIMAT0020956) and other species homologues or orthologues are included.
- the hsa-miR-4433a-5p gene is described in Jim DD et al., 2010, Blood. 116, e118-e127.
- “hsa-miR-4433a-5p” is known as “hsa-mir-4433a” (miRBase Accession No. MI0016773, SEQ ID NO: 478) having a hairpin-like structure as a precursor.
- hsa-miR-3666 gene or “hsa-miR-3666” refers to the hsa-miR-3666 gene (miRBase Accession No. MIMAT0018088) described in SEQ ID NO: 80 or other biological species. Homologs or orthologs are included.
- the hsa-miR-3666 gene is described in Xie X et al., 2005, Nature. 434, 338-345.
- hsa-miR-3666 “hsa-mir-3666” (miRBase Accession No. MI0016067, SEQ ID NO: 479) having a hairpin-like structure as a precursor is known.
- hsa-miR-3186-3p gene or “hsa-miR-3186-3p” refers to the hsa-miR-3186-3p gene described in SEQ ID NO: 81 (miRBase Accession No. MIMAT0015068) and other species homologs or orthologs.
- the hsa-miR-3186-3p gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- “hsa-miR-3186-3p” is known as “hsa-mir-3186” (miRBase Accession No. MI0014229, SEQ ID NO: 480) having a hairpin-like structure as a precursor.
- hsa-miR-4725-5p gene or “hsa-miR-4725-5p” refers to the hsa-miR-4725-5p gene described in SEQ ID NO: 82 (miRBase Accession No. MIMAT0019843) and other species homologs or orthologs.
- the hsa-miR-4725-5p gene is described in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “Hsa-miR-4725-5p” is known as “hsa-mir-4725” (miRBase Accession No. MI0017362, SEQ ID NO: 431) having a hairpin-like structure as a precursor.
- hsa-miR-4488 gene or “hsa-miR-4488” refers to the hsa-miR-4488 gene (miRBase Accession No. MIMAT0019022) described in SEQ ID NO: 83 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4488 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-miR-4488 is known as “hsa-mir-4488” (miRBase Accession No. MI0016849, SEQ ID NO: 481) having a hairpin-like structure as a precursor.
- hsa-miR-4474-3p gene or “hsa-miR-4474-3p” refers to the hsa-miR-4474-3p gene described in SEQ ID NO: 84 (miRBase Accession No. MIMAT0019001) and other species homologues or orthologues are included.
- the hsa-miR-4474-3p gene is described in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4474 (miRBase Accession No. MI0016826, SEQ ID NO: 482) having a hairpin-like structure as a precursor is known.
- hsa-miR-6731-3p gene or “hsa-miR-6731-3p” refers to the hsa-miR-6731-3p gene described in SEQ ID NO: 85 (miRBase Accession No. MIMAT0027364) and other species homologues or orthologues are included.
- the hsa-miR-6731-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6731-3p” is known as “hsa-mir-6731” (miRBase Accession No. MI0022576, SEQ ID NO: 483) having a hairpin-like structure as a precursor.
- hsa-miR-4640-3p gene or “hsa-miR-4640-3p” refers to the hsa-miR-4640-3p gene described in SEQ ID NO: 86 (miRBase Accession No. MIMAT0019700) and other species homologs or orthologs.
- the hsa-miR-4640-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4640-3p “hsa-mir-4640” (miRBase Accession No. MI0017267, SEQ ID NO: 484) having a hairpin-like structure as a precursor is known.
- hsa-miR-202-5p gene or “hsa-miR-202-5p” refers to the hsa-miR-202-5p gene described in SEQ ID NO: 87 (miRBase Accession No. MIMAT0002810) and other species homologues or orthologues are included.
- the hsa-miR-202-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-202-5p “hsa-mir-202” (miRBase Accession No. MI0003130, SEQ ID NO: 485) having a hairpin-like structure as a precursor is known.
- hsa-miR-6816-5p gene or “hsa-miR-6816-5p” refers to the hsa-miR-6816-5p gene described in SEQ ID NO: 88 (miRBase Accession No. MIMAT0027532) and other species homologues or orthologues are included.
- the hsa-miR-6816-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6816-5p” is known as “hsa-mir-6816” (miRBase Accession No. MI0022661, SEQ ID NO: 486), which has a hairpin-like structure as a precursor.
- hsa-miR-638 gene or “hsa-miR-638” refers to the hsa-miR-638 gene (miRBase Accession No. MIMAT0003308) described in SEQ ID NO: 89 or other species. Homologs or orthologs are included. The hsa-miR-638 gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692. In addition, “hsa-miR-638” is known as “hsa-mir-638” (miRBase Accession No. MI0003653, SEQ ID NO: 487) having a hairpin-like structure as a precursor.
- hsa-miR-6821-5p gene or “hsa-miR-6821-5p” refers to the hsa-miR-6821-5p gene described in SEQ ID NO: 90 (miRBase Accession No. MIMAT0027542) and other species homologues or orthologues are included.
- the hsa-miR-6821-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6821-5p” is known as “hsa-mir-6821” (miRBase Accession No. MI0022666, SEQ ID NO: 488) having a hairpin-like structure as a precursor.
- hsa-miR-1247-3p gene or “hsa-miR-1247-3p” refers to the hsa-miR-1247-3p gene described in SEQ ID NO: 91 (miRBase Accession No. MIMAT0022721) and other species homologues or orthologues are included.
- the hsa-miR-1247-3p gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- “hsa-miR-1247-3p” is known as “hsa-mir-1247” (miRBase Accession No. MI0006382, SEQ ID NO: 489) having a hairpin-like structure as a precursor.
- hsa-miR-6765-5p gene or “hsa-miR-6765-5p” refers to the hsa-miR-6765-5p gene described in SEQ ID NO: 92 (miRBase Accession No. MIMAT0027430) and other species homologs or orthologs.
- the hsa-miR-6765-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6765-5p “hsa-mir-6765” (miRBase Accession No. MI0022610, SEQ ID NO: 490) having a hairpin-like structure as a precursor is known.
- hsa-miR-6800-5p gene or “hsa-miR-6800-5p” refers to the hsa-miR-6800-5p gene described in SEQ ID NO: 93 (miRBase Accession No. MIMAT0027500) and other species homologs or orthologs.
- the hsa-miR-6800-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6800-5p” is known as “hsa-mir-6800” (miRBase Accession No. MI0022645, SEQ ID NO: 491) having a hairpin-like structure as a precursor.
- hsa-miR-3928-3p gene or “hsa-miR-3928-3p” refers to the hsa-miR-3928-3p gene described in SEQ ID NO: 94 (miRBase Accession No. MIMAT0018205) and other species homologs or orthologs.
- the hsa-miR-3928-3p gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- hsa-miR-3928-3p is known as “hsa-mir-3928” (miRBase Accession No. MI0016438, SEQ ID NO: 492) having a hairpin-like structure as a precursor.
- hsa-miR-3940-5p gene or “hsa-miR-3940-5p” refers to the hsa-miR-3940-5p gene described in SEQ ID NO: 95 (miRBase Accession No. MIMAT0019229) and other species homologues or orthologues are included.
- the hsa-miR-3940-5p gene was obtained from Liao JY et al., 2010, PLoS One. 5, Vol. 5, e10563.
- hsa-miR-3940-5p “hsa-mir-3940” (miRBase Accession No. MI0016597, SEQ ID NO: 493) having a hairpin-like structure as a precursor is known.
- hsa-miR-3960 gene or “hsa-miR-3960” refers to the hsa-miR-3960 gene (miRBase Accession No. MIMAT0019337) described in SEQ ID NO: 96 and other biological species. Homologs or orthologs are included.
- the hsa-miR-3960 gene is described in Hu R et al., 2011, J Biol Chem. 286, 12328-12339.
- hsa-mir-3960 (miRBase Accession No. MI0016964, SEQ ID NO: 494) having a hairpin-like structure as a precursor is known.
- hsa-miR-6775-5p gene or “hsa-miR-6775-5p” refers to the hsa-miR-6775-5p gene described in SEQ ID NO: 97 (miRBase Accession No. MIMAT0027450) and other species homologs or orthologs.
- the hsa-miR-6775-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6775-5p” is known as “hsa-mir-6775” (miRBase Accession No. MI0022620, SEQ ID NO: 495), which has a hairpin-like structure as a precursor.
- hsa-miR-3178 gene or “hsa-miR-3178” refers to the hsa-miR-3178 gene (miRBase Accession No. MIMAT0015055) described in SEQ ID NO: 98 or other biological species. Homologs or orthologs are included. The hsa-miR-3178 gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685. As for “hsa-miR-3178”, “hsa-mir-3178” (miRBase Accession No. MI0014212, SEQ ID NO: 496), which has a hairpin-like structure as a precursor, is known.
- hsa-miR-1202 gene or “hsa-miR- 1202” refers to the hsa-miR- 1202 gene (miRBase Accession No. MIMAT0005865) described in SEQ ID NO: 99 or other species. Homologs or orthologs are included.
- the hsa-miR- 1202 gene is described in Martin S et al., 2008, Leukemia. , Vol. 22, 330-338.
- hsa-miR-1202 is known as “hsa-mir-1220” (miRBase Accession No. MI0006334, SEQ ID NO: 497), which has a hairpin-like structure as a precursor.
- hsa-miR-6790-5p gene or “hsa-miR-6790-5p” refers to the hsa-miR-6790-5p gene described in SEQ ID NO: 100 (miRBase Accession No. MIMAT0027480) and other species homologs or orthologs.
- the hsa-miR-6790-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6790-5p “hsa-mir-6790” (miRBase Accession No. MI0022635, SEQ ID NO: 498) having a hairpin-like structure as a precursor is known.
- hsa-miR-4731-3p gene or “hsa-miR-4731-3p” refers to the hsa-miR-4731-3p gene described in SEQ ID NO: 101 (miRBase Accession No. MIMAT0019854) and other species homologs or orthologs.
- the hsa-miR-4731-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4731-3p “hsa-mir-4731” (miRBase Accession No. MI0017368, SEQ ID NO: 499) having a hairpin-like structure as a precursor is known.
- hsa-miR-2681-3p gene or “hsa-miR-2681-3p” refers to the hsa-miR-2681-3p gene described in SEQ ID NO: 102 (miRBase Accession No. MIMAT0013516) and other species homologues or orthologues are included.
- the hsa-miR-2681-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-2681-3p “hsa-mir-2681” (miRBase Accession No. MI0012062, SEQ ID NO: 500) having a hairpin-like structure as a precursor is known.
- hsa-miR-6758-5p gene or “hsa-miR-6758-5p” refers to the hsa-miR-6758-5p gene described in SEQ ID NO: 103 (miRBase Accession No. MIMAT0027416) and other species homologs or orthologs.
- the hsa-miR-6758-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6758-5p “hsa-mir-6758” (miRBase Accession No. MI0022603, SEQ ID NO: 501) having a hairpin-like structure as a precursor is known.
- hsa-miR-8072 gene or “hsa-miR-8072” refers to the hsa-miR-8072 gene (miRBase Accession No. MIMAT0030999) described in SEQ ID NO: 104 and other biological species. Homologs or orthologs are included.
- the hsa-miR-8072 gene is disclosed in Wang HJ et al., 2013, Shock. 39, 480-487.
- hsa-miR-8072 “hsa-mir-8072” (miRBase Accession No. MI0025908, SEQ ID NO: 502) having a hairpin-like structure as a precursor is known.
- hsa-miR-518d-3p gene or “hsa-miR-518d-3p” refers to the hsa-miR-518d-3p gene described in SEQ ID NO: 105 (miRBase Accession No. MIMAT0002864) and other species homologs or orthologs.
- the hsa-miR-518d-3p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-518d-3p “hsa-mir-518d” (miRBase Accession No. MI0003171, SEQ ID NO: 503) having a hairpin-like structure as a precursor is known.
- hsa-miR-3606-3p gene or “hsa-miR-3606-3p” refers to the hsa-miR-3606-3p gene described in SEQ ID NO: 106 (miRBase Accession No. MIMAT0022965) and other species homologs or orthologs.
- the hsa-miR-3606-3p gene was obtained from Witten D et al., 2010, BMC Biol. , 8, 58.
- hsa-mir-3606 (miRBase Accession No. MI0015996, SEQ ID NO: 504) having a hairpin-like structure as a precursor is known.
- hsa-miR-4800-5p gene or “hsa-miR-4800-5p” refers to the hsa-miR-4800-5p gene described in SEQ ID NO: 107 (miRBase Accession No. MIMAT0019978) and other species homologues or orthologues are included.
- the hsa-miR-4800-5p gene is described in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “Hsa-miR-4800-5p” is known as “hsa-mir-4800” (miRBase Accession No. MI0017448, SEQ ID NO: 505), which has a hairpin-like structure as a precursor.
- hsa-miR-1292-3p gene or “hsa-miR-1292-3p” refers to the hsa-miR-1292-3p gene described in SEQ ID NO: 108 (miRBase Accession No. MIMAT0022948) and other species homologs or orthologs.
- the hsa-miR-1292-3p gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- hsa-miR-1292-3p “hsa-mir-1292” (miRBase Accession No. MI0006433, SEQ ID NO: 506) having a hairpin-like structure as a precursor is known.
- hsa-miR-6784-3p gene or “hsa-miR-6784-3p” refers to the hsa-miR-6784-3p gene described in SEQ ID NO: 109 (miRBase Accession No. MIMAT0027469) and other species homologues or orthologues are included.
- the hsa-miR-6784-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6784-3p “hsa-mir-6784” (miRBase Accession No. MI0022629, SEQ ID NO: 507) having a hairpin-like structure as a precursor is known.
- hsa-miR-4450 gene or “hsa-miR-4450” refers to the hsa-miR-4450 gene (miRBase Accession No. MIMAT0018971) described in SEQ ID NO: 110 or other species. Homologs or orthologs are included.
- the hsa-miR-4450 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4450 (miRBase Accession No. MI0016795, SEQ ID NO: 508) having a hairpin-like structure as a precursor is known.
- hsa-miR-6132 gene or “hsa-miR-6132” refers to the hsa-miR-6132 gene (miRBase Accession No. MIMAT0024616) described in SEQ ID NO: 111 or other biological species. Homologs or orthologs are included.
- the hsa-miR-6132 gene is disclosed in Dannemann M et al., 2012, Genome Biol Evol. 4, Volume 552-564.
- hsa-mir-6132 miRBase Accession No. MI0021277, SEQ ID NO: 509 having a hairpin-like structure as a precursor is known.
- hsa-miR-4716-5p gene or “hsa-miR-4716-5p” refers to the hsa-miR-4716-5p gene described in SEQ ID NO: 112 (miRBase Accession No. MIMAT0019826) and other species homologues or orthologues are included.
- the hsa-miR-4716-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4716-5p “hsa-mir-4716” (miRBase Accession No. MI0017350, SEQ ID NO: 510) having a hairpin-like structure as a precursor is known.
- hsa-miR-6860 gene or “hsa-miR-6860” refers to the hsa-miR-6860 gene (miRBase Accession No. MIMAT0027622) described in SEQ ID NO: 113 and other biological species. Homologs or orthologs are included.
- the hsa-miR-6860 gene was found in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6860 “hsa-mir-6860” (miRBase Accession No. MI0022707, SEQ ID NO: 511) having a hairpin-like structure as a precursor is known.
- hsa-miR-1268b gene or “hsa-miR-1268b” refers to the hsa-miR-1268b gene (miRBase Accession No. MIMAT0018925) described in SEQ ID NO: 114 or other biological species. Homologs or orthologs are included.
- the hsa-miR-1268b gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-miR-1268b is known as “hsa-mir-1268b” (miRBase Accession No. MI0016748, SEQ ID NO: 512) having a hairpin-like structure as a precursor.
- hsa-miR-378d gene or “hsa-miR-378d” refers to the hsa-miR-378d gene (miRBase Accession No. MIMAT0018926) described in SEQ ID NO: 115 or other biological species. Homologs or orthologs are included.
- the hsa-miR-378d gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- “Hsa-miR-378d” has a hairpin-like structure as a precursor thereof, “hsa-mir-378d-1, hsa-mir-378d-2” (miRBase Accession No. MI0016749, MI0003840, SEQ ID NO: 513, 514) is known.
- hsa-miR-4701-5p gene or “hsa-miR-4701-5p” refers to the hsa-miR-4701-5p gene described in SEQ ID NO: 116 (miRBase Accession No. MIMAT0019798) and other species homologs or orthologs.
- the hsa-miR-4701-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4701-5p “hsa-mir-4701” (miRBase Accession No. MI0017334, SEQ ID NO: 515) having a hairpin-like structure as a precursor is known.
- hsa-miR-4329 gene or “hsa-miR-4329” refers to the hsa-miR-4329 gene (miRBase Accession No. MIMAT0016923) described in SEQ ID NO: 117 or other biological species. Homologs or orthologs are included. The hsa-miR-4329 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. In addition, “hsa-miR-4329” is known as “hsa-mir-4329” (miRBase Accession No. MI0015901, SEQ ID NO: 516) having a hairpin-like structure as a precursor.
- hsa-miR-185-3p gene or “hsa-miR-185-3p” refers to the hsa-miR-185-3p gene described in SEQ ID NO: 118 (miRBase Accession No. MIMAT0004611) and other species homologs or orthologs.
- the hsa-miR-185-3p gene was obtained from Lagos-Quintana M et al., 2003, RNA. 9, 175-179.
- hsa-miR-185-3p “hsa-mir-185” (miRBase Accession No. MI000000482, SEQ ID NO: 517) having a hairpin-like structure as a precursor is known.
- hsa-miR-552-3p gene or “hsa-miR-552-3p” refers to the hsa-miR-552-3p gene described in SEQ ID NO: 119 (miRBase Accession No. MIMAT0003215) and other species homologues or orthologues are included.
- the hsa-miR-552-3p gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- “hsa-miR-552-3p” is known as “hsa-mir-552” (miRBase Accession No. MI0003557, SEQ ID NO: 518) having a hairpin-like structure as a precursor.
- hsa-miR-1273g-5p gene or “hsa-miR-1273g-5p” refers to the hsa-miR-1273g-5p gene described in SEQ ID NO: 120 (miRBase Accession No. MIMAT0020602) and other species homologs or orthologs.
- the hsa-miR-1273g-5p gene is described in Reshmi G et al., 2011, Genomics. 97, 333-340.
- hsa-miR-1273g-5p “hsa-mir-1273g” (miRBase Accession No. MI0018003, SEQ ID NO: 519) having a hairpin-like structure as a precursor is known.
- hsa-miR-6769b-3p gene or “hsa-miR-6769b-3p” refers to the hsa-miR-6769b-3p gene described in SEQ ID NO: 121 (miRBase Accession No. MIMAT0027621) and other species homologues or orthologues are included.
- the hsa-miR-6769b-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6769b-3p “hsa-mir-6769b” (miRBase Accession No. MI0022706, SEQ ID NO: 520) having a hairpin-like structure as a precursor is known.
- hsa-miR-520a-3p gene or “hsa-miR-520a-3p” refers to the hsa-miR-520a-3p gene described in SEQ ID NO: 122 (miRBase Accession No. MIMAT0002834) and other species homologs or orthologs.
- the hsa-miR-520a-3p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-520a-3p” is known as “hsa-mir-520a” (miRBase Accession No. MI0003149, SEQ ID NO: 521) having a hairpin-like structure as a precursor.
- hsa-miR-4524b-5p gene or “hsa-miR-4524b-5p” refers to the hsa-miR-4524b-5p gene described in SEQ ID NO: 123 (miRBase Accession No. MIMAT0022255) and other species homologues or orthologues are included.
- the hsa-miR-4524b-5p gene is described in Tandon M et al., 2012, Oral Dis. 18 and 127-131.
- “hsa-miR-4524b-5p” is known as “hsa-mir-4524b” (miRBase Accession No. MI0019114, SEQ ID NO: 522) having a hairpin-like structure as a precursor.
- hsa-miR-4291 gene or “hsa-miR-4291” refers to the hsa-miR-4291 gene (miRBase Accession No. MIMAT0016922) described in SEQ ID NO: 124 or other biological species. Homologs or orthologs are included. The hsa-miR-4291 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-4291”, “hsa-mir-4291” (miRBase Accession No. MI0015900, SEQ ID NO: 523) having a hairpin-like structure as a precursor is known.
- hsa-miR-6734-3p gene or “hsa-miR-6734-3p” refers to the hsa-miR-6734-3p gene described in SEQ ID NO: 125 (miRBase Accession No. MIMAT0027370) and other species homologues or orthologues are included.
- the hsa-miR-6734-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6734-3p” is known as “hsa-mir-6734” (miRBase Accession No. MI0022579, SEQ ID NO: 524) having a hairpin-like structure as a precursor.
- hsa-miR-143-5p gene or “hsa-miR-143-5p” refers to the hsa-miR-143-5p gene described in SEQ ID NO: 126 (miRBase Accession No. MIMAT0004599) and other species homologs or orthologs.
- the hsa-miR-143-5p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- “Hsa-miR-143-5p” is known as “hsa-mir-143” (miRBase Accession No. MI000059, SEQ ID NO: 525) having a hairpin-like structure as a precursor.
- hsa-miR-939-3p gene or “hsa-miR-939-3p” refers to the hsa-miR-939-3p gene described in SEQ ID NO: 127 (miRBase Accession No. MIMAT0022939) and other species homologues or orthologues are included.
- the hsa-miR-939-3p gene is disclosed in Lui WO et al., 2007, Cancer Res. 67, 6031-6043.
- “hsa-miR-939-3p” is known as “hsa-mir-939” (miRBase Accession No. MI0005761, SEQ ID NO: 526) having a hairpin-like structure as a precursor.
- hsa-miR-6889-3p gene or “hsa-miR-6889-3p” refers to the hsa-miR-6889-3p gene (miRBase Accession No. MIMAT0027679) and other species homologues or orthologues are included.
- the hsa-miR-6889-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6889-3p” is known as “hsa-mir-6889” (miRBase Accession No. MI0022736, SEQ ID NO: 527) having a hairpin-like structure as a precursor.
- hsa-miR-6842-3p gene or “hsa-miR-6842-3p” refers to the hsa-miR-6842-3p gene described in SEQ ID NO: 129 (miRBase Accession No. MIMAT0027587) and other species homologs or orthologs.
- the hsa-miR-6842-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-mir-6842 miRBase Accession No. MI0022688, SEQ ID NO: 528) having a hairpin-like structure as a precursor is known.
- hsa-miR-4511 gene or “hsa-miR-4511” refers to the hsa-miR-4511 gene (miRBase Accession No. MIMAT0019048) described in SEQ ID NO: 130 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4511 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4511 (miRBase Accession No. MI0016877, SEQ ID NO: 529) having a hairpin-like structure as a precursor is known.
- hsa-miR-4318 gene or “hsa-miR-4318” refers to the hsa-miR-4318 gene (miRBase Accession No. MIMAT0016869) described in SEQ ID NO: 131 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4318 gene was obtained from Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192.
- hsa-miR-4318 “hsa-mir-4318” (miRBase Accession No. MI0015847, SEQ ID NO: 530) having a hairpin-like structure as a precursor is known.
- hsa-miR-4653-5p gene or “hsa-miR-4653-5p” refers to the hsa-miR-4653-5p gene (miRBase Accession No. MIMAT0019718) and other species homologues or orthologues are included.
- the hsa-miR-4653-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4653-5p “hsa-mir-4653” (miRBase Accession No. MI0017281, SEQ ID NO: 531) having a hairpin-like structure as a precursor is known.
- hsa-miR-6867-3p gene or “hsa-miR-6867-3p” refers to the hsa-miR-6867-3p gene described in SEQ ID NO: 133 (miRBase Accession No. MIMAT0027635) and other species homologs or orthologs.
- the hsa-miR-6867-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6867-3p” is known as “hsa-mir-6867” (miRBase Accession No. MI0022714, SEQ ID NO: 532) having a hairpin-like structure as a precursor.
- hsa-miR-133b gene or “hsa-miR-133b” refers to the hsa-miR-133b gene (miRBase Accession No. MIMAT000070) described in SEQ ID NO: 134 and other biological species. Homologs or orthologs are included.
- the hsa-miR-133b gene is described in Lim LP et al., 2003, Science. 299, 1540.
- “hsa-miR-133b” is known as “hsa-mir-133b” (miRBase Accession No. MI000022, SEQ ID NO: 533) having a hairpin-like structure as a precursor.
- hsa-miR-3196 gene or “hsa-miR-3196” refers to the hsa-miR-3196 gene (miRBase Accession No. MIMAT0015080) described in SEQ ID NO: 135 and other biological species. Homologs or orthologs are included.
- the hsa-miR-3196 gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- hsa-miR-3196 “hsa-mir-3196” (miRBase Accession No. MI0014241, SEQ ID NO: 534) having a hairpin-like structure as a precursor is known.
- hsa-miR-193b-3p gene or “hsa-miR-193b-3p” refers to the hsa-miR-193b-3p gene described in SEQ ID NO: 136 (miRBase Accession No. MIMAT0002819) and other species homologs or orthologs.
- the hsa-miR-193b-3p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-193b-3p “hsa-mir-193b” (miRBase Accession No. MI0003137, SEQ ID NO: 535) having a hairpin-like structure as a precursor is known.
- hsa-miR-3162-3p gene or “hsa-miR-3162-3p” refers to the hsa-miR-3162-3p gene described in SEQ ID NO: 137 (miRBase Accession No. MIMAT0019213) and other species homologs or orthologs.
- the hsa-miR-3162-3p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “Hsa-miR-3162-3p” is known as “hsa-mir-3162” (miRBase Accession No. MI0014192, SEQ ID NO: 536) having a hairpin-like structure as a precursor.
- hsa-miR-6819-3p gene or “hsa-miR-6819-3p” refers to the hsa-miR-6819-3p gene described in SEQ ID NO: 138 (miRBase Accession No. MIMAT0027539) and other species homologs or orthologs.
- the hsa-miR-6819-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6819-3p” is known as “hsa-mir-6819” (miRBase Accession No. MI0022664, SEQ ID NO: 537) having a hairpin-like structure as a precursor.
- hsa-miR-1908-3p gene or “hsa-miR-1908-3p” refers to the hsa-miR-1908-3p gene described in SEQ ID NO: 139 (miRBase Accession No. MIMAT0026916) and other species homologs or orthologs.
- the hsa-miR-1908-3p gene is described in Bar M et al., 2008, Stem Cells. 26, 2496-2505.
- hsa-miR-1908-3p “hsa-mir-1908” (miRBase Accession No. MI0008329, SEQ ID NO: 538) having a hairpin-like structure as a precursor is known.
- hsa-miR-6786-5p gene or “hsa-miR-6786-5p” refers to the hsa-miR-6786-5p gene described in SEQ ID NO: 140 (miRBase Accession No. MIMAT0027472) and other species homologues or orthologues are included.
- the hsa-miR-6786-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6786-5p “hsa-mir-6786” (miRBase Accession No. MI0022631, SEQ ID NO: 539) having a hairpin-like structure as a precursor is known.
- hsa-miR-3648 gene or “hsa-miR-3648” refers to the hsa-miR-3648 gene (miRBase Accession No. MIMAT0018068) described in SEQ ID NO: 141 or other biological species. Homologs or orthologs are included. The hsa-miR-3648 gene was found in Meiri E et al., 2010, Nucleic Acids Res. 38, 6234-6246.
- “Hsa-miR-3648” has a hairpin-like structure as its precursor, “hsa-mir-3648-1, hsa-mir-3648-2” (miRBase Accession No. MI0016048, MI0031512, SEQ ID NO: 540, 541) is known.
- hsa-miR-4513 gene or “hsa-miR-4513” refers to the hsa-miR-4513 gene (miRBase Accession No. MIMAT0019050) described in SEQ ID NO: 142 or other species. Homologs or orthologs are included.
- the hsa-miR-4513 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4513 (miRBase Accession No. MI0016879, SEQ ID NO: 542) having a hairpin-like structure as a precursor is known.
- hsa-miR-3652 gene or “hsa-miR-3652” refers to the hsa-miR-3652 gene (miRBase Accession No. MIMAT0018072) described in SEQ ID NO: 143 or other biological species. Homologs or orthologs are included. The hsa-miR-3652 gene was found in Meiri E et al., 2010, Nucleic Acids Res. 38, 6234-6246. As for “hsa-miR-3652”, “hsa-mir-3652” (miRBase Accession No. MI0016052, SEQ ID NO: 543) having a hairpin-like structure as a precursor is known.
- hsa-miR-4640-5p gene or “hsa-miR-4640-5p” refers to the hsa-miR-4640-5p gene described in SEQ ID NO: 144 (miRBase Accession No. MIMAT0019699) and other species homologs or orthologs.
- the hsa-miR-4640-5p gene is described in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4640-5p “hsa-mir-4640” (miRBase Accession No. MI0017267, SEQ ID NO: 484) having a hairpin-like structure as a precursor is known.
- hsa-miR-6871-5p gene or “hsa-miR-6871-5p” refers to the hsa-miR-6871-5p gene described in SEQ ID NO: 145 (miRBase Accession No. MIMAT0027642) and other species homologues or orthologues are included.
- the hsa-miR-6871-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “Hsa-miR-6871-5p” is known as “hsa-mir-6871” (miRBase Accession No. MI0022718, SEQ ID NO: 544) having a hairpin-like structure as a precursor.
- hsa-miR-7845-5p gene or “hsa-miR-7845-5p” refers to the hsa-miR-7845-5p gene described in SEQ ID NO: 146 (miRBase Accession No. MIMAT0030420) and other species homologs or orthologs.
- the hsa-miR-7845-5p gene was found in Ple H et al., 2012, PLoS One. 7, Vol. 7, e50746.
- hsa-miR-7845-5p “hsa-mir-7845” (miRBase Accession No. MI0025515, SEQ ID NO: 545) having a hairpin-like structure as a precursor is known.
- hsa-miR-3138 gene or “hsa-miR-3138” refers to the hsa-miR-3138 gene (miRBase Accession No. MIMAT0015006) described in SEQ ID NO: 147 or other biological species. Homologs or orthologs are included. The hsa-miR-3138 gene was found in Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637. In addition, “hsa-miR-3138” is known as “hsa-mir-3138” (miRBase Accession No. MI0014161, SEQ ID NO: 546) having a hairpin-like structure as a precursor.
- hsa-miR-6884-5p gene or “hsa-miR-6884-5p” refers to the hsa-miR-6884-5p gene described in SEQ ID NO: 148 (miRBase Accession No. MIMAT0027668) and other species homologues or orthologues are included.
- the hsa-miR-6884-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6844-5p” is known as “hsa-mir-6844” (miRBase Accession No. MI0022731, SEQ ID NO: 547) having a hairpin-like structure as a precursor.
- hsa-miR-4653-3p gene or “hsa-miR-4653-3p” refers to the hsa-miR-4653-3p gene described in SEQ ID NO: 149 (miRBase Accession No. MIMAT0019719) and other species homologues or orthologues are included.
- the hsa-miR-4653-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4653-3p” is known as “hsa-mir-4653” (miRBase Accession No. MI0017281, SEQ ID NO: 531) having a hairpin-like structure as a precursor.
- hsa-miR-636 gene or “hsa-miR-636” refers to the hsa-miR-636 gene (miRBase Accession No. MIMAT0003306) described in SEQ ID NO: 150 or other biological species. Homologs or orthologs are included. The hsa-miR-636 gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692. In addition, “hsa-miR-636” is known as “hsa-mir-636” (miRBase Accession No. MI0003651, SEQ ID NO: 548) having a hairpin-like structure as a precursor.
- hsa-miR-4652-3p gene or “hsa-miR-4652-3p” refers to the hsa-miR-4652-3p gene described in SEQ ID NO: 151 (miRBase Accession No. MIMAT0019717) and other species homologues or orthologues are included.
- the hsa-miR-4652-3p gene is described in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4652-3p” is known as “hsa-mir-4652” (miRBase Accession No. MI0017280, SEQ ID NO: 549) having a hairpin-like structure as a precursor.
- hsa-miR-6823-5p gene or “hsa-miR-6823-5p” refers to the hsa-miR-6823-5p gene described in SEQ ID NO: 152 (miRBase Accession No. MIMAT0027546) and other species homologues or orthologues are included.
- the hsa-miR-6823-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6823-5p “hsa-mir-6823” (miRBase Accession No. MI0022668, SEQ ID NO: 550) having a hairpin-like structure as a precursor is known.
- hsa-miR-4502 gene or “hsa-miR-4502” refers to the hsa-miR-4502 gene (miRBase Accession No. MIMAT0019038) described in SEQ ID NO: 153 or other species. Homologs or orthologs are included.
- the hsa-miR-4502 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- “Hsa-miR-4502” is known as “hsa-mir-4502” (miRBase Accession No. MI0016865, SEQ ID NO: 551), which has a hairpin-like structure as a precursor.
- hsa-miR-7113-5p gene or “hsa-miR-7113-5p” refers to the hsa-miR-7113-5p gene described in SEQ ID NO: 154 (miRBase Accession No. MIMAT0028123) and other species homologues or orthologues are included.
- the hsa-miR-7113-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-7113-5p is known as “hsa-mir-7113” (miRBase Accession No. MI0022964, SEQ ID NO: 552) having a hairpin-like structure as a precursor.
- hsa-miR-8087 gene or “hsa-miR-8087” refers to the hsa-miR-8087 gene (miRBase Accession No. MIMAT0031014) described in SEQ ID NO: 155 or other biological species. Homologs or orthologs are included.
- the hsa-miR-8087 gene is described in Wang HJ et al., 2013, Shock. 39, 480-487.
- hsa-miR-8087 “hsa-mir-8087” (miRBase Accession No. MI0025923, SEQ ID NO: 553) having a hairpin-like structure as a precursor is known.
- hsa-miR-7154-3p gene or “hsa-miR-7154-3p” refers to the hsa-miR-7154-3p gene described in SEQ ID NO: 156 (miRBase Accession No. MIMAT0028219) and other species homologues or orthologues are included.
- the hsa-miR-7154-3p gene is described in Meunier J et al., 2013, Genome Res. 23, 34-45.
- “hsa-miR-7154-3p” is known as “hsa-mir-7154” (miRBase Accession No. MI0023614, SEQ ID NO: 554) having a hairpin-like structure as a precursor.
- hsa-miR-5189-5p gene or “hsa-miR-5189-5p” refers to the hsa-miR-5189-5p gene described in SEQ ID NO: 157 (miRBase Accession No. MIMAT0021120) and other species homologs or orthologs.
- the hsa-miR-5189-5p gene was obtained from Schotte D et al., 2011, Leukemia. 25, 1389-1399.
- hsa-miR-5189-5p “hsa-mir-5189” (miRBase Accession No. MI0018168, SEQ ID NO: 555) having a hairpin-like structure as a precursor is known.
- hsa-miR-1253 gene or “hsa-miR-1253” refers to the hsa-miR-1253 gene (miRBase Accession No. MIMAT0005904) described in SEQ ID NO: 158 or other biological species. Homologs or orthologs are included.
- the hsa-miR-1253 gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- hsa-mir-1253 miRBase Accession No. MI0006387, SEQ ID NO: 556) having a hairpin-like structure as a precursor is known.
- hsa-miR-518c-5p gene or “hsa-miR-518c-5p” refers to the hsa-miR-518c-5p gene described in SEQ ID NO: 159 (miRBase Accession No. MIMAT0002847) and other species homologs or orthologs.
- the hsa-miR-518c-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-518c-5p” is known as “hsa-mir-518c” (miRBase Accession No. MI0003159, SEQ ID NO: 557) having a hairpin-like structure as a precursor.
- hsa-miR-7151-5p gene or “hsa-miR-7151-5p” refers to the hsa-miR-7151-5p gene described in SEQ ID NO: 160 (miRBase Accession No. MIMAT0028212) and other species homologs or orthologs.
- the hsa-miR-7151-5p gene is described in Meunier J et al., 2013, Genome Res. 23, 34-45.
- hsa-mir-7151 miRBase Accession No. MI0023611, SEQ ID NO: 558 having a hairpin-like structure as a precursor is known.
- hsa-miR-3614-3p gene or “hsa-miR-3614-3p” refers to the hsa-miR-3614-3p gene described in SEQ ID NO: 161 (miRBase Accession No. MIMAT0017993) and other species homologues or orthologues are included.
- the hsa-miR-3614-3p gene was obtained from Witten D et al., 2010, BMC Biol. , 8, 58.
- “hsa-miR-3614-3p” “hsa-mir-3614” (miRBase Accession No. MI0016004, SEQ ID NO: 559) having a hairpin-like structure as a precursor is known.
- hsa-miR-4727-5p gene or “hsa-miR-4727-5p” refers to the hsa-miR-4727-5p gene described in SEQ ID NO: 162 (miRBase Accession No. MIMAT0019847) and other species homologues or orthologues are included.
- the hsa-miR-4727-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4727-5p “hsa-mir-4727” (miRBase Accession No. MI0017364, SEQ ID NO: 560) having a hairpin-like structure as a precursor is known.
- hsa-miR-3682-5p gene or “hsa-miR-3682-5p” refers to the hsa-miR-3682-5p gene described in SEQ ID NO: 163 (miRBase Accession No. MIMAT0019222) and other species homologues or orthologues are included.
- the hsa-miR-3682-5p gene was obtained from Vaz C et al., 2010, BMC Genomics. 11 and 288.
- hsa-miR-3682-5p “hsa-mir-3682” (miRBase Accession No. MI0016083, SEQ ID NO: 561) having a hairpin-like structure as a precursor is known.
- hsa-miR-5090 gene or “hsa-miR-5090” refers to the hsa-miR-5090 gene (miRBase Accession No. MIMAT0021082) described in SEQ ID NO: 164 or other biological species. Homologs or orthologs are included.
- the hsa-miR-5090 gene is disclosed in Ding N et al., 2011, J Radiat Res. 52, 425-432.
- hsa-miR-5090 “hsa-mir-5090” (miRBase Accession No. MI0017979, SEQ ID NO: 562) having a hairpin-like structure as a precursor is known.
- hsa-miR-337-3p gene or “hsa-miR-337-3p” refers to the hsa-miR-337-3p gene (miRBase Accession No. 165 described in SEQ ID NO: 165). MIMAT0000754) and other species homologs or orthologs.
- the hsa-miR-337-3p gene was found in Kim J et al., 2004, Proc Natl Acad Sci USA. 101, 360-365.
- hsa-mir-337 (miRBase Accession No. MI00000806, SEQ ID NO: 563) having a hairpin-like structure as a precursor is known.
- hsa-miR-488-5p gene or “hsa-miR-488-5p” refers to the hsa-miR-488-5p gene described in SEQ ID NO: 166 (miRBase Accession No. MIMAT0002804) and other species homologues or orthologues are included.
- the hsa-miR-488-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-488-5p “hsa-mir-488” (miRBase Accession No. MI0003123, SEQ ID NO: 564), which has a hairpin-like structure as a precursor, is known.
- hsa-miR-100-5p gene or “hsa-miR-100-5p” refers to the hsa-miR-100-5p gene described in SEQ ID NO: 167 (miRBase Accession No. MIMAT00000098) and other species homologs or orthologs.
- the hsa-miR-100-5p gene is described in Mouretos Z et al., 2002, Genes Dev. 16, 720-728.
- “hsa-miR-100-5p” is known as “hsa-mir-100” (miRBase Accession No. MI0000102, SEQ ID NO: 565) having a hairpin-like structure as a precursor.
- hsa-miR-4520-3p gene or “hsa-miR-4520-3p” refers to the hsa-miR-4520-3p gene described in SEQ ID NO: 168 (miRBase Accession No. MIMAT0019057) and other species homologs or orthologs.
- the hsa-miR-4520-3p gene is described in Jim DD et al., 2010, Blood. 116, e118-e127.
- “hsa-miR-4520-3p” is known as “hsa-mir-4520-1” (miRBase Accession No. MI0016886, SEQ ID NO: 566) having a hairpin-like structure as a precursor.
- hsa-miR-373-3p gene or “hsa-miR-373-3p” refers to the hsa-miR-373-3p gene described in SEQ ID NO: 169 (miRBase Accession No. MIMAT000026) and other species homologues or orthologues are included.
- the hsa-miR-373-3p gene was obtained from Suh MR et al., 2004, Dev Biol. 270, 488-498.
- “hsa-miR-373-3p” is known as “hsa-mir-373” (miRBase Accession No. MI0000811, SEQ ID NO: 567) having a hairpin-like structure as a precursor.
- hsa-miR-6499-5p gene or “hsa-miR-6499-5p” refers to the hsa-miR-6499-5p gene described in SEQ ID NO: 170 (miRBase Accession No. MIMAT0025450) and other species homologs or orthologs.
- the hsa-miR-6499-5p gene was obtained from Joyce CE et al., 2011, Hum Mol Genet. 20, Vol. 4025-4040.
- “hsa-miR-6499-5p” is known as “hsa-mir-6499” (miRBase Accession No. MI0022209, SEQ ID NO: 568) having a hairpin-like structure as a precursor.
- hsa-miR-3909 gene or “hsa-miR-3909” refers to the hsa-miR-3909 gene (miRBase Accession No. MIMAT0018183) described in SEQ ID NO: 171 or other biological species. Homologs or orthologs are included.
- the hsa-miR-3909 gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- hsa-miR-3909 “hsa-mir-3909” (miRBase Accession No. MI0016413, SEQ ID NO: 569) having a hairpin-like structure as a precursor is known.
- hsa-miR-32-5p gene or “hsa-miR-32-5p” refers to the hsa-miR-32-5p gene described in SEQ ID NO: 172 (miRBase Accession No. MIMAT000090) and other species homologs or orthologs.
- the hsa-miR-32-5p gene is disclosed in Lagos-Quintana M et al., 2001, Science. 294, 853-858.
- “Hsa-miR-32-5p” is known as “hsa-mir-32” (miRBase Accession No. MI00000090, SEQ ID NO: 570) having a hairpin-like structure as a precursor.
- hsa-miR-302a-3p gene or “hsa-miR-302a-3p” refers to the hsa-miR-302a-3p gene (miRBase Accession No. 173 described in SEQ ID NO: 173). MIMAT0000684) and other species homologs or orthologs.
- the hsa-miR-302a-3p gene was obtained from Houbevy HB et al., 2003, Dev Cell. No. 5, 351-358.
- hsa-mir-302a (miRBase Accession No. MI000038, SEQ ID NO: 571) having a hairpin-like structure as a precursor is known.
- hsa-miR-4686 gene or “hsa-miR-4686” refers to the hsa-miR-4686 gene (miRBase Accession No. MIMAT0019773) described in SEQ ID NO: 174 or other biological species. Homologs or orthologs are included. The hsa-miR-4686 gene was found in Persson H et al., 2011, Cancer Res. 71, 78-86. As for “hsa-miR-4686”, “hsa-mir-4686” (miRBase Accession No. MI0017318, SEQ ID NO: 572) having a hairpin-like structure as a precursor is known.
- hsa-miR-4659a-3p gene or “hsa-miR-4659a-3p” refer to the hsa-miR-4659a-3p gene described in SEQ ID NO: 175 (miRBase Accession No. MIMAT0019727) and other species homologues or orthologues are included.
- the hsa-miR-4659a-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4659a-3p” “hsa-mir-4659a” (miRBase Accession No. MI0017287, SEQ ID NO: 573) having a hairpin-like structure as a precursor is known.
- hsa-miR-4287 gene or “hsa-miR-4287” refers to the hsa-miR-4287 gene (miRBase Accession No. MIMAT0016917) described in SEQ ID NO: 176 or other biological species. Homologs or orthologs are included. The hsa-miR-4287 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-4287”, “hsa-mir-4287” (miRBase Accession No. MI0015895, SEQ ID NO: 574) having a hairpin-like structure as a precursor is known.
- hsa-miR-1301-5p gene or “hsa-miR-1301-5p” refers to the hsa-miR-1301-5p gene described in SEQ ID NO: 177 (miRBase Accession No. MIMAT0026639) and other species homologs or orthologs.
- the hsa-miR-1301-5p gene is described in Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-mir-1301 miRBase Accession No. MI0003815, SEQ ID NO: 575 having a hairpin-like structure as a precursor is known.
- hsa-miR-593-3p gene or “hsa-miR-593-3p” refers to the hsa-miR-593-3p gene described in SEQ ID NO: 178 (miRBase Accession No. MIMAT0004802) and other species homologues or orthologues are included.
- the hsa-miR-593-3p gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- hsa-miR-593-3p “hsa-mir-593” (miRBase Accession No. MI0003605, SEQ ID NO: 576) having a hairpin-like structure as a precursor is known.
- hsa-miR-517a-3p gene or “hsa-miR-517a-3p” refers to the hsa-miR-517a-3p gene described in SEQ ID NO: 179 (miRBase Accession No. MIMAT0002852) and other species homologues or orthologues are included.
- the hsa-miR-517a-3p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-517a-3p “hsa-mir-517a” (miRBase Accession No. MI0003161, SEQ ID NO: 577) having a hairpin-like structure as a precursor is known.
- hsa-miR-517b-3p gene or “hsa-miR-517b-3p” refers to the hsa-miR-517b-3p gene described in SEQ ID NO: 180 (miRBase Accession No. MIMAT0002857) and other species homologs or orthologs.
- the hsa-miR-517b-3p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-517b-3p “hsa-mir-517b” (miRBase Accession No. MI0003165, SEQ ID NO: 578) having a hairpin-like structure as a precursor is known.
- hsa-miR-142-3p gene or “hsa-miR-142-3p” refers to the hsa-miR-142-3p gene described in SEQ ID NO: 181 (miRBase Accession No. MIMAT000034) and other species homologues or orthologues are included.
- the hsa-miR-142-3p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- “hsa-miR-142-3p” is known as “hsa-mir-142” (miRBase Accession No. MI0000458, SEQ ID NO: 579) having a hairpin-like structure as a precursor.
- hsa-miR-1185-2-3p gene or “hsa-miR-1185-2-3p” as used herein refers to the hsa-miR-1185-2-3p described in SEQ ID NO: 182. Genes (miRBBase Accession No. MIMAT0022713) and other species homologues or orthologues are included.
- the hsa-miR-1185-2-3p gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-mir-1185-2 miRBase Accession No. MI0003821, SEQ ID NO: 580 having a hairpin-like structure as a precursor is known.
- hsa-miR-602 gene or “hsa-miR-602” refers to the hsa-miR-602 gene (miRBase Accession No. MIMAT0003270) described in SEQ ID NO: 183 or other biological species. Homologs or orthologs are included.
- the hsa-miR-602 gene was obtained from Cummins JM et al., 2006, Proc Natl Acad Sci U SA. 103, 3687-3692.
- hsa-miR-602 “hsa-mir-602” (miRBase Accession No. MI0003615, SEQ ID NO: 581) having a hairpin-like structure as a precursor is known.
- hsa-miR-527 gene or “hsa-miR-527” refers to the hsa-miR-527 gene (miRBase Accession No. MIMAT0002862) described in SEQ ID NO: 184 or other biological species. Homologs or orthologs are included.
- the hsa-miR-527 gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- hsa-miR-527 “hsa-mir-527” (miRBase Accession No. MI0003179, SEQ ID NO: 582) having a hairpin-like structure as a precursor is known.
- hsa-miR-518a-5p gene or “hsa-miR-518a-5p” refers to the hsa-miR-518a-5p gene described in SEQ ID NO: 185 (miRBase Accession No. MIMAT0005457) and other species homologues or orthologues are included.
- the hsa-miR-518a-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “Hsa-miR-518a-5p” has a hairpin-like structure as a precursor thereof, “hsa-mir-518a-1, hsa-mir-518a-2” (miRBase Accession No. MI0003170, MI0003173, SEQ ID NO: 583, 584) is known.
- hsa-miR-4682 gene or “hsa-miR-4682” refers to the hsa-miR-4682 gene (miRBase Accession No. MIMAT0019767) described in SEQ ID NO: 186 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4682 gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4682” is known as “hsa-mir-4682” (miRBase Accession No. MI0017314, SEQ ID NO: 585), which has a hairpin-like structure as a precursor.
- hsa-miR-28-5p gene or “hsa-miR-28-5p” refers to the hsa-miR-28-5p gene (miRBase Accession No. 187 described in SEQ ID NO: 187). MIMAT0000085) and other species homologs or orthologs.
- the hsa-miR-28-5p gene is described in Lagos-Quintana M et al., 2001, Science. 294, 853-858.
- “hsa-miR-28-5p” is known as “hsa-mir-28” (miRBase Accession No. MI0000086, SEQ ID NO: 586) having a hairpin-like structure as a precursor.
- hsa-miR-4252 gene or “hsa-miR-4252” refers to the hsa-miR-4252 gene (miRBase Accession No. MIMAT0016886) described in SEQ ID NO: 188 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4252 gene was obtained from Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192.
- hsa-miR-4252 “hsa-mir-4252” (miRBase Accession No. MI0015864, SEQ ID NO: 587) having a hairpin-like structure as a precursor is known.
- hsa-miR-452-5p gene or “hsa-miR-452-5p” refers to the hsa-miR-452-5p gene described in SEQ ID NO: 189 (miRBase Accession No. MIMAT001635) and other species homologs or orthologs.
- the hsa-miR-452-5p gene was obtained from Altvia Y et al., 2005, Nucleic Acids Res. 33, 2697-2706.
- “hsa-miR-452-5p” is known as “hsa-mir-452” (miRBase Accession No. MI0001733, SEQ ID NO: 588) having a hairpin-like structure as a precursor.
- hsa-miR-525-5p gene or “hsa-miR-525-5p” refers to the hsa-miR-525-5p gene described in SEQ ID NO: 190 (miRBase Accession No. MIMAT0002838) and other species homologs or orthologs.
- the hsa-miR-525-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-525-5p” is known as “hsa-mir-525” (miRBase Accession No. MI0003152, SEQ ID NO: 589) having a hairpin-like structure as a precursor.
- hsa-miR-3622a-3p gene or “hsa-miR-3622a-3p” refers to the hsa-miR-3622a-3p gene (miRBase Accession No. MIMAT0018004) and other species homologs or orthologs.
- the hsa-miR-3622a-3p gene was obtained from Witten D et al., 2010, BMC Biol. , 8, 58.
- “hsa-miR-3622a-3p” is known as “hsa-mir-3622a” (miRBase Accession No. MI0016013, SEQ ID NO: 590) having a hairpin-like structure as a precursor.
- hsa-miR-6813-3p gene or “hsa-miR-6813-3p” refers to the hsa-miR-6813-3p gene described in SEQ ID NO: 192 (miRBase Accession No. MIMAT0027527) and other species homologues or orthologues are included.
- the hsa-miR-6813-3p gene was obtained from Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “Hsa-miR-6813-3p” is known as “hsa-mir-6683” (miRBase Accession No. MI0022658, SEQ ID NO: 591) having a hairpin-like structure as a precursor.
- hsa-miR-4769-3p gene or “hsa-miR-4769-3p” refers to the hsa-miR-4769-3p gene described in SEQ ID NO: 193 (miRBase Accession No. MIMAT0019923) and other species homologues or orthologues are included.
- the hsa-miR-4769-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4769-3p “hsa-mir-4769” (miRBase Accession No. MI0017410, SEQ ID NO: 592) having a hairpin-like structure as a precursor is known.
- hsa-miR-5698 gene or “hsa-miR-5698” refers to the hsa-miR-5698 gene (miRBase Accession No. MIMAT0022491) described in SEQ ID NO: 194 or other biological species. Homologs or orthologs are included.
- the hsa-miR-5698 gene was obtained from Watahiki A et al., 2011, PLoS One. 6, Volume 24, e24950.
- hsa-miR-5698 “hsa-mir-5698” (miRBase Accession No. MI0019305, SEQ ID NO: 593) having a hairpin-like structure as a precursor is known.
- hsa-miR-1915-3p gene or “hsa-miR-1915-3p” refers to the hsa-miR-1915-3p gene described in SEQ ID NO: 195 (miRBase Accession No. MIMAT0007892) and other species homologues or orthologues are included.
- the hsa-miR-1915-3p gene is described in Bar M et al., 2008, Stem Cells. 26, 2496-2505.
- “hsa-miR-1915-3p” is known as “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 594) having a hairpin-like structure as a precursor.
- hsa-miR-1343-5p gene or “hsa-miR-1343-5p” refers to the hsa-miR-1343-5p gene described in SEQ ID NO: 196 (miRBase Accession No. MIMAT0027038) and other species homologs or orthologs.
- the hsa-miR-1343-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-1343-5p” is known as “hsa-mir-1343” (miRBase Accession No. MI0017320, SEQ ID NO: 595) having a hairpin-like structure as a precursor.
- hsa-miR-6861-5p gene or “hsa-miR-6861-5p” refers to the hsa-miR-6861-5p gene described in SEQ ID NO: 197 (miRBase Accession No. MIMAT0027623) and other species homologues or orthologues are included.
- the hsa-miR-6861-5p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6861-5p “hsa-mir-6861” (miRBase Accession No. MI0022708, SEQ ID NO: 596) having a hairpin-like structure as a precursor is known.
- hsa-miR-6781-5p gene or “hsa-miR-6781-5p” refers to the hsa-miR-6781-5p gene described in SEQ ID NO: 198 (miRBase Accession No. MIMAT0027462) and other species homologues or orthologues are included.
- the hsa-miR-6781-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6781-5p” is known as “hsa-mir-6781” (miRBase Accession No. MI0022626, SEQ ID NO: 597) having a hairpin-like structure as a precursor.
- hsa-miR-4508 gene or “hsa-miR-4508” refers to the hsa-miR-4508 gene (miRBase Accession No. MIMAT0019045) described in SEQ ID NO: 199 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4508 gene is described in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4508 (miRBase Accession No. MI0016872, SEQ ID NO: 598) having a hairpin-like structure as a precursor is known.
- hsa-miR-6743-5p gene or “hsa-miR-6743-5p” refers to the hsa-miR-6743-5p gene described in SEQ ID NO: 200 (miRBase Accession No. MIMAT0027387) and other species homologues or orthologues are included.
- the hsa-miR-6743-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6743-5p” is known as “hsa-mir-6743” (miRBase Accession No. MI0022588, SEQ ID NO: 599) having a hairpin-like structure as a precursor.
- hsa-miR-6726-5p gene or “hsa-miR-6726-5p” refers to the hsa-miR-6726-5p gene described in SEQ ID NO: 201 (miRBase Accession No. MIMAT0027353) and other species homologues or orthologues are included.
- the hsa-miR-6726-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6726-5p “hsa-mir-6726” (miRBase Accession No. MI0022571, SEQ ID NO: 600) having a hairpin-like structure as a precursor is known.
- hsa-miR-4525 gene or “hsa-miR-4525” refers to the hsa-miR-4525 gene (miRBase Accession No. MIMAT0019064) described in SEQ ID NO: 202 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4525 gene is disclosed in Jim DD et al., 2010, Blood. 116, e118-e127.
- hsa-mir-4525 (miRBase Accession No. MI0016892, SEQ ID NO: 601) having a hairpin-like structure as a precursor is known.
- hsa-miR-4651 gene or “hsa-miR-4651” refers to the hsa-miR-4651 gene (miRBase Accession No. MIMAT0019715) described in SEQ ID NO: 203 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4651 gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “Hsa-miR-4651” is known as “hsa-mir-4651” (miRBase Accession No. MI0017279, SEQ ID NO: 602) having a hairpin-like structure as a precursor.
- hsa-miR-6813-5p gene or “hsa-miR-6813-5p” refers to the hsa-miR-6813-5p gene described in SEQ ID NO: 204 (miRBase Accession No. MIMAT0027526) and other species homologues or orthologues are included.
- the hsa-miR-6813-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6813-5p” is known as “hsa-mir-6683” (miRBase Accession No. MI0022658, SEQ ID NO: 591) having a hairpin-like structure as a precursor.
- hsa-miR-5787 gene or “hsa-miR-5787” refers to the hsa-miR-5787 gene (miRBase Accession No. MIMAT0023252) described in SEQ ID NO: 205 or other biological species. Homologs or orthologs are included. The hsa-miR-5787 gene was obtained from Yoo H et al., 2011, Biochem Biophys Res Commun. 415, 567-572. In addition, “hsa-miR-5787” is known as “hsa-mir-5787” (miRBase Accession No. MI0019797, SEQ ID NO: 603) having a hairpin-like structure as a precursor.
- hsa-miR-1290 gene or “hsa-miR-1290” refers to the hsa-miR-1290 gene (miRBase Accession No. MIMAT0005880) described in SEQ ID NO: 206 and other biological species. Homologs or orthologs are included.
- the hsa-miR-1290 gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- “Hsa-miR-1290” is known as “hsa-mir-1290” (miRBase Accession No. MI0006352, SEQ ID NO: 604) having a hairpin-like structure as a precursor.
- hsa-miR-6075 gene or “hsa-miR-6075” refers to the hsa-miR-6075 gene (miRBase Accession No. MIMAT0023700) described in SEQ ID NO: 207 or other biological species. Homologs or orthologs are included. The hsa-miR-6075 gene was found in Voellenkle C et al., 2012, RNA. 18, 472-484. Also, “hsa-miR-6075” is known as “hsa-mir-6075” (miRBase Accession No. MI0020352, SEQ ID NO: 605) having a hairpin-like structure as a precursor.
- hsa-miR-4758-5p gene or “hsa-miR-4758-5p” refers to the hsa-miR-4758-5p gene described in SEQ ID NO: 208 (miRBase Accession No. MIMAT0019903) and other species homologues or orthologues are included.
- the hsa-miR-4758-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4758-5p “hsa-mir-4758” (miRBase Accession No. MI0017399, SEQ ID NO: 606) having a hairpin-like structure as a precursor is known.
- hsa-miR-4690-5p gene or “hsa-miR-4690-5p” refers to the hsa-miR-4690-5p gene described in SEQ ID NO: 209 (miRBase Accession No. MIMAT0019779) and other species homologs or orthologs.
- the hsa-miR-4690-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4690-5p “hsa-mir-4690” (miRBase Accession No. MI0017323, SEQ ID NO: 607) having a hairpin-like structure as a precursor is known.
- hsa-miR-762 gene or “hsa-miR-762” refers to the hsa-miR-762 gene (miRBase Accession No. MIMAT0010313) described in SEQ ID NO: 210 or other biological species. Homologs or orthologs are included.
- the hsa-miR-762 gene was obtained from Berezkov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-miR-762 “hsa-mir-762” (miRBase Accession No. MI0003892, SEQ ID NO: 608) having a hairpin-like structure as a precursor is known.
- hsa-miR-1225-3p gene or “hsa-miR-1225-3p” refers to the hsa-miR-1225-3p gene described in SEQ ID NO: 211 (miRBase Accession No. MIMAT0005573) and other species homologues or orthologues are included.
- the hsa-miR-1225-3p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- “hsa-miR-1225-3p” is known as “hsa-mir-1225” (miRBase Accession No. MI0006311, SEQ ID NO: 609) having a hairpin-like structure as a precursor.
- hsa-miR-3184-5p gene or “hsa-miR-3184-5p” refers to the hsa-miR-3184-5p gene (miRBase Accession No. MIMAT0015064) and other species homologs or orthologs.
- the hsa-miR-3184-5p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “Hsa-miR-3184-5p” is known as “hsa-mir-3184” (miRBase Accession No. MI0014226, SEQ ID NO: 398) having a hairpin-like structure as a precursor.
- hsa-miR-665 gene or “hsa-miR-665” refers to the hsa-miR-665 gene (miRBase Accession No. MIMAT0004952) described in SEQ ID NO: 213 or other biological species. A homolog or ortholog is included.
- the hsa-miR-665 gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- “Hsa-miR-665” is known as “hsa-mir-665” (miRBase Accession No. MI0005563, SEQ ID NO: 610) having a hairpin-like structure as a precursor.
- hsa-miR-211-5p gene or “hsa-miR-211-5p” refers to the hsa-miR-211-5p gene described in SEQ ID NO: 214 (miRBase Accession No. MIMAT0000268) and other species homologues or orthologues are included.
- the hsa-miR-211-5p gene is described in Lim LP et al., 2003, Science. 299, 1540.
- hsa-mir-211 miRBase Accession No. MI000027, SEQ ID NO: 611 having a hairpin-like structure as a precursor is known.
- hsa-miR-1247-5p gene or “hsa-miR-1247-5p” refers to the hsa-miR-1247-5p gene described in SEQ ID NO: 215 (miRBase Accession No. MIMAT0005899) and other species homologues or orthologues are included.
- the hsa-miR-1247-5p gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- “hsa-miR-1247-5p” is known as “hsa-mir-1247” (miRBase Accession No. MI0006382, SEQ ID NO: 489) having a hairpin-like structure as a precursor.
- hsa-miR-3656 gene or “hsa-miR-3656” refers to the hsa-miR-3656 gene (miRBase Accession No. MIMAT0018076) described in SEQ ID NO: 216 or other biological species. Homologs or orthologs are included. The hsa-miR-3656 gene was found in Meiri E et al., 2010, Nucleic Acids Res. 38, 6234-6246. As for “hsa-miR-3656”, “hsa-mir-3656” (miRBase Accession No. MI0016056, SEQ ID NO: 612) having a hairpin-like structure as a precursor is known.
- hsa-miR-149-5p gene or “hsa-miR-149-5p” refers to the hsa-miR-149-5p gene described in SEQ ID NO: 217 (miRBase Accession No. MIMAT000050) and other species homologs or orthologs.
- the hsa-miR-149-5p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- hsa-miR-149-5p “hsa-mir-149” (miRBase Accession No. MI0000478, SEQ ID NO: 613) having a hairpin-like structure as a precursor is known.
- hsa-miR-744-5p gene or “hsa-miR-744-5p” refers to the hsa-miR-744-5p gene described in SEQ ID NO: 218 (miRBase Accession No. MIMAT0004945) and other species homologs or orthologs.
- the hsa-miR-744-5p gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-miR-744-5p is known as “hsa-mir-744” (miRBase Accession No. MI0005559, SEQ ID NO: 614) having a hairpin-like structure as a precursor.
- hsa-miR-345-5p gene or “hsa-miR-345-5p” refers to the hsa-miR-345-5p gene described in SEQ ID NO: 219 (miRBase Accession No. MIMAT0000772) and other species homologs or orthologs.
- the hsa-miR-345-5p gene was found in Kim J et al., 2004, Proc Natl Acad Sci U SA. 101, 360-365.
- hsa-mir-345 (miRBase Accession No. MI000025, SEQ ID NO: 615) having a hairpin-like structure as a precursor is known.
- hsa-miR-150-5p gene or “hsa-miR-150-5p” refers to the hsa-miR-150-5p gene described in SEQ ID NO: 220 (miRBase Accession No. MIMAT0000451) and other species homologues or orthologues are included.
- the hsa-miR-150-5p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- “hsa-miR-150-5p” is known as “hsa-mir-150” (miRBase Accession No. MI000079, SEQ ID NO: 616) having a hairpin-like structure as a precursor.
- hsa-miR-191-3p gene or “hsa-miR-191-3p” refers to the hsa-miR-191-3p gene described in SEQ ID NO: 221 (miRBase Accession No. MIMAT001618) and other species homologs or orthologs.
- the hsa-miR-191-3p gene was obtained from Lagos-Quintana M et al., 2003, RNA. 9, 175-179.
- “hsa-miR-191-3p” is known as “hsa-mir-191” (miRBase Accession No. MI000065, SEQ ID NO: 617) having a hairpin-like structure as a precursor.
- hsa-miR-651-5p gene or “hsa-miR-651-5p” refers to the hsa-miR-651-5p gene (miRBase Accession No. MIMAT0003321) and other species homologues or orthologues are included.
- the hsa-miR-651-5p gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- “hsa-miR-651-5p” is known as “hsa-mir-651” (miRBase Accession No. MI0003666, SEQ ID NO: 618) having a hairpin-like structure as a precursor.
- hsa-miR-34a-5p gene or “hsa-miR-34a-5p” refers to the hsa-miR-34a-5p gene described in SEQ ID NO: 223 (miRBase Accession No. MIMAT 0000255) and other species homologs or orthologs.
- the hsa-miR-34a-5p gene is disclosed in Dostie J et al., 2003, RNA. 9, Vol. 180-186.
- hsa-mir-34a (miRBase Accession No. MI0000268, SEQ ID NO: 619) having a hairpin-like structure as a precursor is known.
- hsa-miR-409-5p gene or “hsa-miR-409-5p” refers to the hsa-miR-409-5p gene described in SEQ ID NO: 224 (miRBase Accession No. MIMAT001638) and other species homologs or orthologs.
- the hsa-miR-409-5p gene was obtained from Altvia Y et al., 2005, Nucleic Acids Res. 33, 2697-2706.
- “hsa-miR-409-5p” is known as “hsa-mir-409” (miRBase Accession No. MI0001735, SEQ ID NO: 620) having a hairpin-like structure as a precursor.
- hsa-miR-369-5p gene or “hsa-miR-369-5p” refers to the hsa-miR-369-5p gene described in SEQ ID NO: 225 (miRBase Accession No. MIMAT0001621) and other species homologs or orthologs are included.
- the hsa-miR-369-5p gene was obtained from Suh MR et al., 2004, Dev Biol. 270, 488-498.
- hsa-miR-369-5p “hsa-mir-369” (miRBase Accession No. MI000077, SEQ ID NO: 621) having a hairpin-like structure as a precursor is known.
- hsa-miR-1915-5p gene or “hsa-miR-1915-5p” refers to the hsa-miR-1915-5p gene described in SEQ ID NO: 226 (miRBase Accession No. MIMAT0007891) and other species homologues or orthologues are included.
- the hsa-miR-1915-5p gene is described in Bar M et al., 2008, Stem Cells. 26, 2496-2505.
- “hsa-miR-1915-5p” is known as “hsa-mir-1915” (miRBase Accession No. MI0008336, SEQ ID NO: 594) having a hairpin-like structure as a precursor.
- hsa-miR-204-5p gene or “hsa-miR-204-5p” refers to the hsa-miR-204-5p gene described in SEQ ID NO: 227 (miRBase Accession No. MIMAT0000265) and other species homologues or orthologues are included.
- the hsa-miR-204-5p gene is described in Lim LP et al., 2003, Science. 299, 1540.
- “hsa-miR-204-5p” is known as “hsa-mir-204” (miRBase Accession No. MI00000028, SEQ ID NO: 622) having a hairpin-like structure as a precursor.
- hsa-miR-137 gene or “hsa-miR-137” refers to the hsa-miR-137 gene (miRBase Accession No. MIMAT000029) described in SEQ ID NO: 228 or other species. Homologs or orthologs are included.
- the hsa-miR-137 gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- “hsa-miR-137” is known as “hsa-mir-137” (miRBase Accession No. MI0000454, SEQ ID NO: 623) having a hairpin-like structure as a precursor.
- hsa-miR-382-5p gene or “hsa-miR-382-5p” refers to the hsa-miR-382-5p gene described in SEQ ID NO: 229 (miRBase Accession No. MIMAT0000737) and other species homologs or orthologs.
- the hsa-miR-382-5p gene was obtained from Altvia Y et al., 2005, Nucleic Acids Res. 33, 2697-2706.
- hsa-miR-382-5p “hsa-mir-382” (miRBase Accession No. MI000070, SEQ ID NO: 624) having a hairpin-like structure as a precursor is known.
- hsa-miR-517-5p gene or “hsa-miR-517-5p” refers to the hsa-miR-517-5p gene described in SEQ ID NO: 230 (miRBase Accession No. MIMAT0002851) and other species homologues or orthologues are included.
- the hsa-miR-517-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-517-5p” is known as “hsa-mir-517c” (miRBase Accession No. MI0003174, SEQ ID NO: 625) having a hairpin-like structure as a precursor.
- hsa-miR-532-5p gene or “hsa-miR-532-5p” refers to the hsa-miR-532-5p gene described in SEQ ID NO: 231 (miRBase Accession No. MIMAT0002888) and other species homologs or orthologs.
- the hsa-miR-532-5p gene is described in Lagos-Quintana M et al., 2001, Science. 294, 853-858.
- hsa-miR-532-5p “hsa-mir-532” (miRBase Accession No. MI0003205, SEQ ID NO: 626) having a hairpin-like structure as a precursor is known.
- hsa-miR-22-5p gene or “hsa-miR-22-5p” refers to the hsa-miR-22-5p gene described in SEQ ID NO: 232 (miRBase Accession No. MIMAT0004495) and other species homologs or orthologs.
- the hsa-miR-22-5p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- hsa-miR-22-5p is known as “hsa-mir-22” (miRBase Accession No. MI0000078, SEQ ID NO: 627) having a hairpin-like structure as a precursor.
- hsa-miR-1237-3p gene or “hsa-miR-1237-3p” refers to the hsa-miR-1237-3p gene described in SEQ ID NO: 233 (miRBase Accession No. MIMAT0005592) and other species homologs or orthologs.
- the hsa-miR-1237-3p gene is described in Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-mir-1237 (miRBase Accession No. MI0006327, SEQ ID NO: 628) having a hairpin-like structure as a precursor is known.
- hsa-miR-1224-3p gene or “hsa-miR-1224-3p” refers to the hsa-miR-1224-3p gene described in SEQ ID NO: 234 (miRBase Accession No. MIMAT0005459) and other species homologs or orthologs.
- the hsa-miR-1224-3p gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- hsa-miR-1224-3p “hsa-mir-1224” (miRBase Accession No. MI0003764, SEQ ID NO: 629) having a hairpin-like structure as a precursor is known.
- hsa-miR-625-3p gene or “hsa-miR-625-3p” refers to the hsa-miR-625-3p gene described in SEQ ID NO: 235 (miRBase Accession No. MIMAT0004808) and other species homologues or orthologues are included.
- the hsa-miR-625-3p gene was found in Kim J et al., 2004, Proc Natl Acad Sci USA. 101, 360-365.
- “hsa-miR-625-3p” is known as “hsa-mir-625” (miRBase Accession No. MI0003639, SEQ ID NO: 630) having a hairpin-like structure as a precursor.
- hsa-miR-328-3p gene or “hsa-miR-328-3p” refer to the hsa-miR-328-3p gene described in SEQ ID NO: 236 (miRBase Accession No. MIMAT0000752) and other species homologs or orthologs.
- the hsa-miR-328-3p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- “hsa-miR-328-3p” is known as “hsa-mir-328” (miRBase Accession No. MI000004, SEQ ID NO: 631) having a hairpin-like structure as a precursor.
- hsa-miR-122-5p gene or “hsa-miR-122-5p” refers to the hsa-miR-122-5p gene described in SEQ ID NO: 237 (miRBase Accession No. MIMAT000021) and other species homologues or orthologues are included.
- the hsa-miR-122-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-122-5p” is known as “hsa-mir-122” (miRBase Accession No. MI000042, SEQ ID NO: 632) having a hairpin-like structure as a precursor.
- hsa-miR-202-3p gene or “hsa-miR-202-3p” refers to the hsa-miR-202-3p gene described in SEQ ID NO: 238 (miRBase Accession No. MIMAT0002811) and other species homologues or orthologues are included.
- the hsa-miR-202-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-202-3p” is known as “hsa-mir-202” (miRBase Accession No. MI0003130, SEQ ID NO: 485) having a hairpin-like structure as a precursor.
- hsa-miR-4781-5p gene or “hsa-miR-4781-5p” refers to the hsa-miR-4781-5p gene described in SEQ ID NO: 239 (miRBase Accession No. MIMAT0019942) and other species homologues or orthologues are included.
- the hsa-miR-4781-5p gene was obtained from Artzi S et al., 2008, BMC Bioinformatics. , 9, 39.
- “hsa-miR-4781-5p” is known as “hsa-mir-4781” (miRBase Accession No. MI0017426, SEQ ID NO: 633) having a hairpin-like structure as a precursor.
- hsa-miR-718 gene or “hsa-miR-718” refers to the hsa-miR-718 gene (miRBase Accession No. MIMAT0012735) described in SEQ ID NO: 240 or other biological species. Homologs or orthologs are included. The hsa-miR-718 gene was found in Kim J et al., 2004, Proc Natl Acad Sci US A. 101, 360-365. Also, “hsa-miR-718” is known as “hsa-mir-718” (miRBase Accession No. MI0012489, SEQ ID NO: 634) having a hairpin-like structure as a precursor.
- hsa-miR-342-3p gene or “hsa-miR-342-3p” refers to the hsa-miR-342-3p gene described in SEQ ID NO: 241 (miRBase Accession No. MIMAT000053) and other species homologues or orthologues are included.
- the hsa-miR-342-3p gene is described in Lagos-Quintana M et al., 2001, Science. 294, 853-858.
- hsa-miR-342-3p “hsa-mir-342” (miRBase Accession No. MI000005, SEQ ID NO: 635) having a hairpin-like structure as a precursor is known.
- hsa-miR-26b-3p gene or “hsa-miR-26b-3p” refers to the hsa-miR-26b-3p gene described in SEQ ID NO: 242 (miRBase Accession No. MIMAT0004500) and other species homologs or orthologs.
- the hsa-miR-26b-3p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. 12, Vol. 735-739.
- hsa-miR-26b-3p “hsa-mir-26b” (miRBase Accession No. MI0000084, SEQ ID NO: 636) having a hairpin-like structure as a precursor is known.
- hsa-miR-140-3p gene or “hsa-miR-140-3p” refer to the hsa-miR-140-3p gene described in SEQ ID NO: 243 (miRBase Accession No. MIMAT0004597) and other species homologues or orthologues are included.
- the hsa-miR-140-3p gene was obtained from Lagos-Quintana M et al., 2003, RNA. 9, 175-179.
- hsa-mir-140 (miRBase Accession No. MI000056, SEQ ID NO: 637) having a hairpin-like structure as a precursor is known.
- hsa-miR-200a-3p gene or “hsa-miR-200a-3p” refers to the hsa-miR-200a-3p gene described in SEQ ID NO: 244 (miRBase Accession No. MIMAT000002) and other species homologues or orthologues are included.
- the hsa-miR-200a-3p gene was found in Kasshima K et al., 2004, Biochem Biophys Res Commun. 322, 403-410.
- “hsa-miR-200a-3p” is known as “hsa-mir-200a” (miRBase Accession No. MI0000737, SEQ ID NO: 638) having a hairpin-like structure as a precursor.
- hsa-miR-378a-3p gene or “hsa-miR-378a-3p” refers to the hsa-miR-378a-3p gene described in SEQ ID NO: 245 (miRBase Accession No. MIMAT000072) and other species homologues or orthologues are included.
- the hsa-miR-378a-3p gene was obtained from Fu H et al., 2005, FEBS Lett. 579, 3849-3854.
- “hsa-miR-378a-3p” is known as “hsa-mir-378a” (miRBase Accession No. MI000086, SEQ ID NO: 639) having a hairpin-like structure as a precursor.
- hsa-miR-484 gene or “hsa-miR-484” refers to the hsa-miR-484 gene (miRBase Accession No. MIMAT0002174) described in SEQ ID NO: 246 or other biological species. Homologs or orthologs are included. The hsa-miR-484 gene was obtained from Houbevy HB et al., 2003, Dev Cell. No. 5, 351-358. As for “hsa-miR-484”, “hsa-mir-484” (miRBase Accession No. MI0002468, SEQ ID NO: 640) having a hairpin-like structure as a precursor is known.
- hsa-miR-296-5p gene or “hsa-miR-296-5p” refers to the hsa-miR-296-5p gene described in SEQ ID NO: 247 (miRBase Accession No. MIMAT060690) and other species homologues or orthologues are included.
- the hsa-miR-296-5p gene is described in Lim LP et al., 2003, Science. 299, 1540.
- “hsa-miR-296-5p” is known as “hsa-mir-296” (miRBase Accession No. MI000047, SEQ ID NO: 641) having a hairpin-like structure as a precursor.
- hsa-miR-205-5p gene or “hsa-miR-205-5p” refers to the hsa-miR-205-5p gene described in SEQ ID NO: 248 (miRBase Accession No. MIMAT0000266) and other species homologs or orthologs.
- the hsa-miR-205-5p gene was obtained from Altvia Y et al., 2005, Nucleic Acids Res. 33, 2697-2706.
- “hsa-miR-205-5p” is known as “hsa-mir-205” (miRBase Accession No. MI00000028, SEQ ID NO: 642) having a hairpin-like structure as a precursor.
- hsa-miR-431-5p gene or “hsa-miR-431-5p” refers to the hsa-miR-431-5p gene described in SEQ ID NO: 249 (miRBase Accession No. MIMAT001625) and other species homologs or orthologs.
- the hsa-miR-431-5p gene was obtained from Kawaji H et al., 2008, BMC Genomics. , Vol. 9, 157.
- hsa-mir-431 miRBase Accession No. MI0001721, SEQ ID NO: 643 having a hairpin-like structure as a precursor is known.
- hsa-miR-1471 gene or “hsa-miR-1471” refers to the hsa-miR-1471 gene (miRBase Accession No. MIMAT0007349) described in SEQ ID NO: 250 or other biological species. Homologs or orthologs are included.
- the hsa-miR-1471 gene was obtained from Azuma-Mukai A et al., 2008, Proc Natl Acad Sci US A. 105, 7964-7969.
- hsa-miR-1471 “hsa-mir-1471” (miRBase Accession No. MI00000076, SEQ ID NO: 644) having a hairpin-like structure as a precursor is known.
- hsa-miR-1538 gene or “hsa-miR-1538” refers to the hsa-miR-1538 gene (miRBase Accession No. MIMAT0007400) described in SEQ ID NO: 251 and other biological species. Homologs or orthologs are included. The hsa-miR-1538 gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692. “Hsa-miR-1538” is known as “hsa-mir-1538” (miRBase Accession No. MI0007259, SEQ ID NO: 645), which has a hairpin-like structure as a precursor.
- hsa-miR-449b-3p gene or “hsa-miR-449b-3p” refers to the hsa-miR-449b-3p gene described in SEQ ID NO: 252 (miRBase Accession No. MIMAT0009203) and other species homologues or orthologues are included.
- the hsa-miR-449b-3p gene was obtained from Schotte D et al., 2009, Leukemia. , Volume 23, 313-322.
- hsa-mir-449b (miRBase Accession No. MI0003673, SEQ ID NO: 646) having a hairpin-like structure as a precursor is known.
- hsa-miR-1976 gene or “hsa-miR-1976” refers to the hsa-miR-1976 gene (miRBase Accession No. MIMAT0009451) described in SEQ ID NO: 253 or other biological species. Homologs or orthologs are included. The hsa-miR-1976 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-1976”, “hsa-mir-1976” (miRBase Accession No. MI0009986, SEQ ID NO: 647) having a hairpin-like structure as a precursor is known.
- hsa-miR-4268 gene or “hsa-miR-4268” refers to the hsa-miR-4268 gene (miRBase Accession No. MIMAT0016896) described in SEQ ID NO: 254 and other biological species. Homologs or orthologs are included. The hsa-miR-4268 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. Also, “hsa-miR-4268” is known as “hsa-mir-4268” (miRBase Accession No. MI0015874, SEQ ID NO: 648) having a hairpin-like structure as a precursor.
- hsa-miR-4279 gene or “hsa-miR-4279” refers to the hsa-miR-4279 gene (miRBase Accession No. MIMAT0016909) described in SEQ ID NO: 255 and other biological species. Homologs or orthologs are included.
- the hsa-miR-4279 gene was obtained from Witten D et al., 2010, BMC Biol. , 8, 58.
- hsa-mir-4279 miRBase Accession No. MI0015887, SEQ ID NO: 649) having a hairpin-like structure as a precursor is known.
- hsa-miR-3620-3p gene or “hsa-miR-3620-3p” refers to the hsa-miR-3620-3p gene described in SEQ ID NO: 256 (miRBase Accession No. MIMAT0018001) and other species homologues or orthologues are included.
- the hsa-miR-3620-3p gene was obtained from Witten D et al., 2010, BMC Biol. , 8, 58.
- “hsa-miR-3620-3p” is known as “hsa-mir-3620” (miRBase Accession No. MI0016011, SEQ ID NO: 650) having a hairpin-like structure as a precursor.
- hsa-miR-3944-3p gene or “hsa-miR-3944-3p” refers to the hsa-miR-3944-3p gene described in SEQ ID NO: 257 (miRBase Accession No. MIMAT0018360) and other species homologues or orthologues are included.
- the hsa-miR-3944-3p gene was obtained from Liao JY et al., 2010, PLoS One. 5, Vol. 5, e10563.
- “hsa-miR-3944-3p” is known as “hsa-mir-3944” (miRBase Accession No. MI0016601, SEQ ID NO: 651) having a hairpin-like structure as a precursor.
- hsa-miR-3156-3p gene or “hsa-miR-3156-3p” refers to the hsa-miR-3156-3p gene described in SEQ ID NO: 258 (miRBase Accession No. MIMAT0019209) and other species homologues or orthologues are included.
- the hsa-miR-3156-3p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “Hsa-miR-3156-3p” has a hairpin-like structure as its precursor, “hsa-mir-3156-1, hsa-mir-3156-2” (miRBase Accession No. MI0014184, MI0014230, SEQ ID NO: 652, 653) is known.
- hsa-miR-3187-5p gene or “hsa-miR-3187-5p” refers to the hsa-miR-3187-5p gene described in SEQ ID NO: 259 (miRBase Accession No. MIMAT0019216) and other species homologs or orthologs are included.
- the hsa-miR-3187-5p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “hsa-miR-3187-5p” is known as “hsa-mir-3187” (miRBase Accession No. MI0014231, SEQ ID NO: 654) having a hairpin-like structure as a precursor.
- hsa-miR-4665-3p gene or “hsa-miR-4687-3p” refers to the hsa-miR-4665-3p gene (miRBase Accession No. MIMAT0019772) and other species homologues or orthologues are included.
- the hsa-miR-4485-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4585-3p” is known as “hsa-mir-4485” (miRBase Accession No. MI0017317, SEQ ID NO: 655) having a hairpin-like structure as a precursor.
- hsa-miR-4695-3p gene or “hsa-miR-4695-3p” refers to the hsa-miR-4695-3p gene described in SEQ ID NO: 261 (miRBase Accession No. MIMAT0019789) and other species homologues or orthologues are included.
- the hsa-miR-4695-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4695-3p “hsa-mir-4695” (miRBase Accession No. MI0017328, SEQ ID NO: 656) having a hairpin-like structure as a precursor is known.
- hsa-miR-4697-3p gene or “hsa-miR-4697-3p” refers to the hsa-miR-4697-3p gene described in SEQ ID NO: 262 (miRBase Accession No. MIMAT0019792) and other species homologues or orthologues are included.
- the hsa-miR-4697-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4697-3p “hsa-mir-4697” (miRBase Accession No. MI0017330, SEQ ID NO: 657) having a hairpin-like structure as a precursor is known.
- hsa-miR-4713-5p gene or “hsa-miR-4713-5p” refers to the hsa-miR-4713-5p gene described in SEQ ID NO: 263 (miRBase Accession No. MIMAT0019820) and other species homologues or orthologues are included.
- the hsa-miR-4713-5p gene is described in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4713-5p “hsa-mir-4713” (miRBase Accession No. MI0017347, SEQ ID NO: 658) having a hairpin-like structure as a precursor is known.
- hsa-miR-4723-3p gene or “hsa-miR-4723-3p” refers to the hsa-miR-4723-3p gene described in SEQ ID NO: 264 (miRBase Accession No. MIMAT0019839) and other species homologs or orthologs.
- the hsa-miR-4723-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4723-3p “hsa-mir-4723” (miRBase Accession No. MI0017359, SEQ ID NO: 659) having a hairpin-like structure as a precursor is known.
- hsa-miR-371b-3p gene or “hsa-miR-371b-3p” refers to the hsa-miR-371b-3p gene described in SEQ ID NO: 265 (miRBase Accession No. MIMAT0019893) and other species homologs or orthologs are included.
- the hsa-miR-371b-3p gene is described in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-371b-3p “hsa-mir-371b” (miRBase Accession No. MI0017393, SEQ ID NO: 660) having a hairpin-like structure as a precursor is known.
- hsa-miR-3151-3p gene or “hsa-miR-3151-3p” refers to the hsa-miR-3151-3p gene described in SEQ ID NO: 266 (miRBase Accession No. MIMAT0027026) and other species homologues or orthologues are included.
- the hsa-miR-3151-3p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “hsa-miR-3151-3p” is known as “hsa-mir-3151” (miRBase Accession No. MI0014178, SEQ ID NO: 661) having a hairpin-like structure as a precursor.
- hsa-miR-3192-3p gene or “hsa-miR-3192-3p” refers to the hsa-miR-3192-3p gene described in SEQ ID NO: 267 (miRBase Accession No. MIMAT0027027) and other species homologs or orthologs.
- the hsa-miR-3192-3p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “hsa-miR-3192-3p” is known as “hsa-mir-3192” (miRBase Accession No. MI0014237, SEQ ID NO: 662) having a hairpin-like structure as a precursor.
- hsa-miR-6728-3p gene or “hsa-miR-6728-3p” refers to the hsa-miR-6728-3p gene described in SEQ ID NO: 268 (miRBase Accession No. MIMAT0027358) and other species homologues or orthologues are included.
- the hsa-miR-6728-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6728-3p” is known as “hsa-mir-6728” (miRBase Accession No. MI0022573, SEQ ID NO: 663) having a hairpin-like structure as a precursor.
- hsa-miR-6736-3p gene or “hsa-miR-6736-3p” refers to the hsa-miR-6736-3p gene described in SEQ ID NO: 269 (miRBase Accession No. MIMAT0027374) and other species homologues or orthologues are included.
- the hsa-miR-6736-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6736-3p” is known as “hsa-mir-6736” (miRBase Accession No. MI0022581, SEQ ID NO: 664) having a hairpin-like structure as a precursor.
- hsa-miR-6740-3p gene or “hsa-miR-6740-3p” refers to the hsa-miR-6740-3p gene described in SEQ ID NO: 270 (miRBase Accession No. MIMAT0027382) and other species homologues or orthologues are included.
- the hsa-miR-6740-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6740-3p” is known as “hsa-mir-6740” (miRBase Accession No. MI0022585, SEQ ID NO: 665) having a hairpin-like structure as a precursor.
- hsa-miR-6741-3p gene or “hsa-miR-6741-3p” refers to the hsa-miR-6741-3p gene described in SEQ ID NO: 271 (miRBase Accession No. MIMAT0027384) and other species homologues or orthologues are included.
- the hsa-miR-6741-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6741-3p” is known as “hsa-mir-6741” (miRBase Accession No. MI0022586, SEQ ID NO: 666) having a hairpin-like structure as a precursor.
- hsa-miR-6743-3p gene or “hsa-miR-6743-3p” refers to the hsa-miR-6743-3p gene (miRBase Accession No. MIMAT0027388) and other species homologs or orthologs.
- the hsa-miR-6743-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6743-3p “hsa-mir-6743” (miRBase Accession No. MI0022588, SEQ ID NO: 599) having a hairpin-like structure as a precursor is known.
- hsa-miR-6747-3p gene or “hsa-miR-6747-3p” refers to the hsa-miR-6747-3p gene described in SEQ ID NO: 273 (miRBase Accession No. MIMAT0027395) and other species homologues or orthologues are included.
- the hsa-miR-6747-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6747-3p “hsa-mir-6747” (miRBase Accession No. MI0022592, SEQ ID NO: 667) having a hairpin-like structure as a precursor is known.
- hsa-miR-6750-3p gene or “hsa-miR-6750-3p” refers to the hsa-miR-6750-3p gene described in SEQ ID NO: 274 (miRBase Accession No. MIMAT0027401) and other species homologs or orthologs.
- the hsa-miR-6750-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6750-3p” is known as “hsa-mir-6750” (miRBase Accession No. MI0022595, SEQ ID NO: 668) having a hairpin-like structure as a precursor.
- hsa-miR-6754-3p gene or “hsa-miR-6754-3p” refers to the hsa-miR-6754-3p gene described in SEQ ID NO: 275 (miRBase Accession No. MIMAT0027409) and other species homologues or orthologues are included.
- the hsa-miR-6754-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6754-3p” is known as “hsa-mir-6754” (miRBase Accession No. MI0022599, SEQ ID NO: 669) having a hairpin-like structure as a precursor.
- hsa-miR-6759-3p gene or “hsa-miR-6759-3p” refers to the hsa-miR-6759-3p gene described in SEQ ID NO: 276 (miRBase Accession No. MIMAT0027419) and other species homologues or orthologues are included.
- the hsa-miR-6759-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6759-3p “hsa-mir-6759” (miRBase Accession No. MI0022604, SEQ ID NO: 670) having a hairpin-like structure as a precursor is known.
- hsa-miR-6761-3p gene or “hsa-miR-6761-3p” refers to the hsa-miR-6761-3p gene described in SEQ ID NO: 277 (miRBase Accession No. MIMAT0027423) and other species homologs or orthologs.
- the hsa-miR-6761-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6761-3p” is known as “hsa-mir-6761” (miRBase Accession No. MI0022606, SEQ ID NO: 671) having a hairpin-like structure as a precursor.
- hsa-miR-6762-3p gene or “hsa-miR-6762-3p” refers to the hsa-miR-6762-3p gene described in SEQ ID NO: 278 (miRBase Accession No. MIMAT0027425) and other species homologues or orthologues are included.
- the hsa-miR-6762-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6762-3p” is known as “hsa-mir-6762” (miRBase Accession No. MI0022607, SEQ ID NO: 672) having a hairpin-like structure as a precursor.
- hsa-miR-6769a-3p gene or “hsa-miR-6769a-3p” refer to the hsa-miR-6769a-3p gene described in SEQ ID NO: 279 (miRBase Accession No. MIMAT0027439) and other species homologues or orthologues are included.
- the hsa-miR-6769a-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6769a-3p “hsa-mir-6769a” (miRBase Accession No. MI0022614, SEQ ID NO: 673), which has a hairpin-like structure as a precursor, is known.
- hsa-miR-6766-3p gene or “hsa-miR-6766-3p” refers to the hsa-miR-6766-3p gene (miRBase Accession No. MIMAT0027453) and other species homologues or orthologues are included.
- the hsa-miR-6767-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6766p is known as “hsa-mir-6766” (miRBase Accession No. MI0022621, SEQ ID NO: 674) having a hairpin-like structure as a precursor.
- hsa-miR-6778-3p gene or “hsa-miR-6778-3p” refers to the hsa-miR-6778-3p gene described in SEQ ID NO: 281 (miRBase Accession No. MIMAT0027457) and other species homologues or orthologues are included.
- the hsa-miR-6778-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6778-3p “hsa-mir-6778” (miRBase Accession No. MI0022623, SEQ ID NO: 675) having a hairpin-like structure as a precursor is known.
- hsa-miR-6679-3p gene or “hsa-miR-6779-3p” refers to the hsa-miR-6679-3p gene described in SEQ ID NO: 282 (miRBase Accession No. MIMAT0027459) and other species homologs or orthologs.
- the hsa-miR-6679-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6779-3p” is known as “hsa-mir-6679” (miRBase Accession No. MI0022624, SEQ ID NO: 676) having a hairpin-like structure as a precursor.
- hsa-miR-6786-3p gene or “hsa-miR-6786-3p” refers to the hsa-miR-6786-3p gene described in SEQ ID NO: 283 (miRBase Accession No. MIMAT0027473) and other species homologues or orthologues are included.
- the hsa-miR-6786-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6786-3p “hsa-mir-6786” (miRBase Accession No. MI0022631, SEQ ID NO: 539) having a hairpin-like structure as a precursor is known.
- hsa-miR-6787-3p gene or “hsa-miR-6787-3p” refers to the hsa-miR-6787-3p gene described in SEQ ID NO: 284 (miRBase Accession No. MIMAT0027475) and other species homologs or orthologs.
- the hsa-miR-6787-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6787-3p “hsa-mir-6787” (miRBase Accession No. MI0022632, SEQ ID NO: 677) having a hairpin-like structure as a precursor is known.
- hsa-miR-6792-3p gene or “hsa-miR-6792-3p” refers to the hsa-miR-6792-3p gene described in SEQ ID NO: 285 (miRBase Accession No. MIMAT0027485) and other species homologues or orthologues are included.
- the hsa-miR-6792-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6792-3p “hsa-mir-6792” (miRBase Accession No. MI0022637, SEQ ID NO: 678) having a hairpin-like structure as a precursor is known.
- hsa-miR-6794-3p gene or “hsa-miR-6794-3p” refers to the hsa-miR-6794-3p gene described in SEQ ID NO: 286 (miRBase Accession No. MIMAT0027489) and other species homologs or orthologs.
- the hsa-miR-6794-3p gene was found in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6794-3p “hsa-mir-6794” (miRBase Accession No. MI0022639, SEQ ID NO: 679) having a hairpin-like structure as a precursor is known.
- hsa-miR-6801-3p gene or “hsa-miR-6801-3p” refers to the hsa-miR-6801-3p gene described in SEQ ID NO: 287 (miRBase Accession No. MIMAT0027503) and other species homologues or orthologues are included.
- the hsa-miR-6801-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6801-3p “hsa-mir-6801” (miRBase Accession No. MI0022646, SEQ ID NO: 680) having a hairpin-like structure as a precursor is known.
- hsa-miR-6802-3p gene or “hsa-miR-6802-3p” refers to the hsa-miR-6802-3p gene described in SEQ ID NO: 288 (miRBase Accession No. MIMAT0027505) and other species homologues or orthologues are included.
- the hsa-miR-6802-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6802-3p” is known as “hsa-mir-6802” (miRBase Accession No. MI0022647, SEQ ID NO: 681) having a hairpin-like structure as a precursor.
- hsa-miR-6803-3p gene or “hsa-miR-6803-3p” refers to the hsa-miR-6803-3p gene described in SEQ ID NO: 289 (miRBase Accession No. MIMAT0027507) and other species homologues or orthologues are included.
- the hsa-miR-6803-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6803-3p” is known as “hsa-mir-6803” (miRBase Accession No. MI0022648, SEQ ID NO: 682) having a hairpin-like structure as a precursor.
- hsa-miR-6804-3p gene or “hsa-miR-6804-3p” refers to the hsa-miR-6804-3p gene described in SEQ ID NO: 290 (miRBase Accession No. MIMAT0027509) and other species homologues or orthologues are included.
- the hsa-miR-6804-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6804-3p “hsa-mir-6804” (miRBase Accession No. MI0022649, SEQ ID NO: 683) having a hairpin-like structure as a precursor is known.
- hsa-miR-6810-5p gene or “hsa-miR-6810-5p” refers to the hsa-miR-6810-5p gene described in SEQ ID NO: 291 (miRBase Accession No. MIMAT0027520) and other species homologues or orthologues are included.
- the hsa-miR-6810-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6810-5p “hsa-mir-6810” (miRBase Accession No. MI0022655, SEQ ID NO: 684) having a hairpin-like structure as a precursor is known.
- hsa-miR-6823-3p gene or “hsa-miR-6823-3p” refers to the hsa-miR-6823-3p gene described in SEQ ID NO: 292 (miRBase Accession No. MIMAT0027547) and other species homologues or orthologues are included.
- the hsa-miR-6823-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6823-3p “hsa-mir-6823” (miRBase Accession No. MI0022668, SEQ ID NO: 550) having a hairpin-like structure as a precursor is known.
- hsa-miR-6825-3p gene or “hsa-miR-6825-3p” refers to the hsa-miR-6825-3p gene described in SEQ ID NO: 293 (miRBase Accession No. MIMAT0027551) and other species homologues or orthologues are included.
- the hsa-miR-6825-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6825-3p “hsa-mir-6825” (miRBase Accession No. MI0022670, SEQ ID NO: 685) having a hairpin-like structure as a precursor is known.
- hsa-miR-6829-3p gene or “hsa-miR-6829-3p” refers to the hsa-miR-6829-3p gene described in SEQ ID NO: 294 (miRBase Accession No. MIMAT0027559) and other species homologues or orthologues are included.
- the hsa-miR-6829-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6829-3p “hsa-mir-6829” (miRBase Accession No. MI0022674, SEQ ID NO: 686) having a hairpin-like structure as a precursor is known.
- hsa-miR-6833-3p gene or “hsa-miR-6833-3p” refers to the hsa-miR-6833-3p gene described in SEQ ID NO: 295 (miRBase Accession No. MIMAT0027567) and other species homologues or orthologues are included.
- the hsa-miR-6833-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6833-3p” is known as “hsa-mir-6833” (miRBase Accession No. MI0022678, SEQ ID NO: 687) having a hairpin-like structure as a precursor.
- hsa-miR-6835-3p gene or “hsa-miR-6834-3p” refers to the hsa-miR-6835-3p gene described in SEQ ID NO: 296 (miRBase Accession No. MIMAT0027569) and other species homologs or orthologs are included.
- the hsa-miR-6835-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6834p” is known as “hsa-mir-6683” (miRBase Accession No. MI0022679, SEQ ID NO: 688) having a hairpin-like structure as a precursor.
- hsa-miR-6780b-3p gene or “hsa-miR-6780b-3p” refers to the hsa-miR-6780b-3p gene described in SEQ ID NO: 297 (miRBase Accession No. MIMAT0027573) and other species homologues or orthologues are included.
- the hsa-miR-6780b-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6780b-3p” is known as “hsa-mir-6780b” (miRBase Accession No. MI0022681, SEQ ID NO: 689) having a hairpin-like structure as a precursor.
- hsa-miR-6845-3p gene or “hsa-miR-6845-3p” refers to the hsa-miR-6845-3p gene described in SEQ ID NO: 298 (miRBase Accession No. MIMAT0027591) and other species homologues or orthologues are included.
- the hsa-miR-6845-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6845-3p “hsa-mir-6845” (miRBase Accession No. MI0022691, SEQ ID NO: 690) having a hairpin-like structure as a precursor is known.
- hsa-miR-6862-3p gene or “hsa-miR-6862-3p” refers to the hsa-miR-6862-3p gene described in SEQ ID NO: 299 (miRBase Accession No. MIMAT0027626) and other species homologues or orthologues are included.
- the hsa-miR-6862-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “Hsa-miR-6862-3p” has a hairpin-like structure as a precursor thereof, “hsa-mir-6686-1, hsa-mir-66862-2” (miRBase Accession No. MI0022709, MI0026415, SEQ ID NO: 691, 692).
- hsa-miR-6865-3p gene or “hsa-miR-6865-3p” refers to the hsa-miR-6865-3p gene described in SEQ ID NO: 300 (miRBase Accession No. MIMAT0027631) and other species homologs or orthologs are included.
- the hsa-miR-6865-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6865-3p “hsa-mir-6865” (miRBase Accession No. MI0022712, SEQ ID NO: 693) having a hairpin-like structure as a precursor is known.
- hsa-miR-6870-3p gene or “hsa-miR-6870-3p” refers to the hsa-miR-6870-3p gene described in SEQ ID NO: 301 (miRBase Accession No. MIMAT0027641) and other species homologues or orthologues are included.
- the hsa-miR-6870-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “Hsa-miR-6870-3p” is known as “hsa-mir-6870” (miRBase Accession No. MI0022717, SEQ ID NO: 694) having a hairpin-like structure as a precursor.
- hsa-miR-6875-3p gene or “hsa-miR-6875-3p” refers to the hsa-miR-6875-3p gene described in SEQ ID NO: 302 (miRBase Accession No. MIMAT0027651) and other species homologues or orthologues are included.
- the hsa-miR-6875-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6875-3p” is known as “hsa-mir-6875” (miRBase Accession No. MI0022722, SEQ ID NO: 695) having a hairpin-like structure as a precursor.
- hsa-miR-6877-3p gene or “hsa-miR-6877-3p” refers to the hsa-miR-6877-3p gene described in SEQ ID NO: 303 (miRBase Accession No. MIMAT0027655) and other species homologues or orthologues are included.
- the hsa-miR-6877-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6877-3p” is known as “hsa-mir-6877” (miRBase Accession No. MI0022724, SEQ ID NO: 696) having a hairpin-like structure as a precursor.
- hsa-miR-6879-3p gene or “hsa-miR-6879-3p” refers to the hsa-miR-6879-3p gene described in SEQ ID NO: 304 (miRBase Accession No. MIMAT0027659) and other species homologues or orthologues are included.
- the hsa-miR-6879-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6879-3p “hsa-mir-6879” (miRBase Accession No. MI0022726, SEQ ID NO: 697) having a hairpin-like structure as a precursor is known.
- hsa-miR-6882-3p gene or “hsa-miR-6882-3p” refers to the hsa-miR-6882-3p gene described in SEQ ID NO: 305 (miRBase Accession No. MIMAT0027665) and other species homologs or orthologs.
- the hsa-miR-6882-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “Hsa-miR-6882-3p” is known as “hsa-mir-6882” (miRBase Accession No. MI0022729, SEQ ID NO: 698) having a hairpin-like structure as a precursor.
- hsa-miR-685-3p gene or “hsa-miR-685-3p” refers to the hsa-miR-685-3p gene described in SEQ ID NO: 306 (miRBase Accession No. MIMAT0027671) and other species homologues or orthologues are included.
- the hsa-miR-685-3p gene was obtained from Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6885-3p “hsa-mir-6885” (miRBase Accession No. MI0022732, SEQ ID NO: 699) having a hairpin-like structure as a precursor is known.
- hsa-miR-6886-3p gene or “hsa-miR-6886-3p” refers to the hsa-miR-6886-3p gene described in SEQ ID NO: 307 (miRBase Accession No. MIMAT0027673) and other species homologues or orthologues are included.
- the hsa-miR-6886-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6886-3p “hsa-mir-6886” (miRBase Accession No. MI0022733, SEQ ID NO: 700) having a hairpin-like structure as a precursor is known.
- hsa-miR-6887-3p gene or “hsa-miR-6887-3p” refers to the hsa-miR-6887-3p gene described in SEQ ID NO: 308 (miRBase Accession No. MIMAT0027675) and other species homologs or orthologs.
- the hsa-miR-6877-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6887-3p” is known as “hsa-mir-6877” (miRBase Accession No. MI0022734, SEQ ID NO: 701) having a hairpin-like structure as a precursor.
- hsa-miR-6890-3p gene or “hsa-miR-6890-3p” refers to the hsa-miR-6890-3p gene described in SEQ ID NO: 309 (miRBase Accession No. MIMAT0027681) and other species homologues or orthologues are included.
- the hsa-miR-6890-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6890-3p” is known as “hsa-mir-6890” (miRBase Accession No. MI0022737, SEQ ID NO: 702) having a hairpin-like structure as a precursor.
- hsa-miR-6893-3p gene or “hsa-miR-6893-3p” refers to the hsa-miR-6893-3p gene described in SEQ ID NO: 310 (miRBase Accession No. MIMAT0027687) and other species homologues or orthologues are included.
- the hsa-miR-6893-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6893-3p” is known as “hsa-mir-6893” (miRBase Accession No. MI0022740, SEQ ID NO: 703) having a hairpin-like structure as a precursor.
- hsa-miR-6894-3p gene or “hsa-miR-6894-3p” refers to the hsa-miR-6894-3p gene (miRBase Accession No. 3) described in SEQ ID NO: 311. MIMAT0027689) and other species homologs or orthologs.
- the hsa-miR-6894-3p gene was found in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6894-3p” is known as “hsa-mir-6894” (miRBase Accession No. MI0022741, SEQ ID NO: 704) having a hairpin-like structure as a precursor.
- hsa-miR-7106-3p gene or “hsa-miR-7106-3p” refers to the hsa-miR-7106-3p gene (miRBase Accession No. 3) described in SEQ ID NO: 312. MIMAT0028110) and other species homologues or orthologues are included.
- the hsa-miR-7106-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-7106-3p” is known as “hsa-mir-7106” (miRBase Accession No. MI0022957, SEQ ID NO: 705) having a hairpin-like structure as a precursor.
- hsa-miR-7109-3p gene or “hsa-miR-7109-3p” refers to the hsa-miR-7109-3p gene described in SEQ ID NO: 313 (miRBase Accession No. MIMAT0028116) and other species homologs or orthologs.
- the hsa-miR-7109-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-mir-7109 (miRBase Accession No. MI0022960, SEQ ID NO: 706) having a hairpin-like structure as a precursor is known.
- hsa-miR-7114-3p gene or “hsa-miR-7114-3p” refers to the hsa-miR-7114-3p gene described in SEQ ID NO: 314 (miRBase Accession No. MIMAT0028126) and other species homologues or orthologues are included.
- the hsa-miR-7114-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-7114-3p” is known as “hsa-mir-7114” (miRBase Accession No. MI0022965, SEQ ID NO: 707), which has a hairpin-like structure as a precursor.
- hsa-miR-7155-5p gene or “hsa-miR-7155-5p” refers to the hsa-miR-7155-5p gene described in SEQ ID NO: 315 (miRBase Accession No. MIMAT0028220) and other species homologs or orthologs.
- the hsa-miR-7155-5p gene is described in Meunier J et al., 2013, Genome Res. 23, 34-45.
- hsa-miR-7155-5p “hsa-mir-7155” (miRBase Accession No. MI0023615, SEQ ID NO: 708) having a hairpin-like structure as a precursor is known.
- hsa-miR-7160-5p gene or “hsa-miR-7160-5p” refers to the hsa-miR-7160-5p gene described in SEQ ID NO: 316 (miRBase Accession No. MIMAT0028230) and other species homologs or orthologs.
- the hsa-miR-7160-5p gene is described in Meunier J et al., 2013, Genome Res. 23, 34-45.
- “hsa-miR-7160-5p” is known as “hsa-mir-7160” (miRBase Accession No. MI0023621, SEQ ID NO: 709) having a hairpin-like structure as a precursor.
- hsa-miR-615-3p gene or “hsa-miR-615-3p” refers to the hsa-miR-615-3p gene described in SEQ ID NO: 317 (miRBase Accession No. MIMAT0003283) and other species homologues or orthologues are included.
- the hsa-miR-615-3p gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- “hsa-miR-615-3p” is known as “hsa-mir-615” (miRBase Accession No. MI0003628, SEQ ID NO: 710) having a hairpin-like structure as a precursor.
- hsa-miR-920 gene or “hsa-miR-920” refers to the hsa-miR-920 gene (miRBase Accession No. MIMAT0004970) described in SEQ ID NO: 318 or other biological species. Homologs or orthologs are included. The hsa-miR-920 gene was found in Novotny GW et al., 2007, Int J Androl. , 30, 316-326. Also, “hsa-miR-920” is known as “hsa-mir-920” (miRBase Accession No. MI0005712, SEQ ID NO: 711) having a hairpin-like structure as a precursor.
- hsa-miR-1825 gene or “hsa-miR-1825” refers to the hsa-miR-1825 gene (miRBase Accession No. MIMAT0006765) described in SEQ ID NO: 319 or other biological species. Homologs or orthologs are included. The hsa-miR-1825 gene was found in Friedlander MR et al., 2008, Nat Biotechnol. 26, 407-415. As for “hsa-miR-1825”, “hsa-mir-1825” (miRBase Accession No. MI0008193, SEQ ID NO: 712) having a hairpin-like structure as a precursor is known.
- hsa-miR-675-3p gene or “hsa-miR-675-3p” refers to the hsa-miR-675-3p gene described in SEQ ID NO: 320 (miRBase Accession No. MIMAT0006790) and other species homologues or orthologues are included.
- the hsa-miR-675-3p gene is disclosed in Cai X et al., 2007, RNA. , Vol. 13, 313-316.
- hsa-mir-675 (miRBase Accession No. MI0005416, SEQ ID NO: 713) having a hairpin-like structure as a precursor is known.
- hsa-miR-1910-5p gene or “hsa-miR-1910-5p” refers to the hsa-miR-1910-5p gene described in SEQ ID NO: 321 (miRBase Accession No. MIMAT0007884) and other species homologues or orthologues are included.
- the hsa-miR-1910-5p gene is described in Bar M et al., 2008, Stem Cells. 26, 2496-2505.
- “hsa-miR-1910-5p” is known as “hsa-mir-1910” (miRBase Accession No. MI0008331, SEQ ID NO: 714) having a hairpin-like structure as a precursor.
- hsa-miR-2278 gene or “hsa-miR-2278” refers to the hsa-miR-2278 gene (miRBase Accession No. MIMAT0011778) described in SEQ ID NO: 322 or other biological species. Homologs or orthologs are included.
- the hsa-miR-2278 gene was obtained from Nygaard S et al., 2009, BMC Med Genomics. 2 and 35.
- hsa-miR-2278 “hsa-mir-2278” (miRBase Accession No. MI0011285, SEQ ID NO: 715) having a hairpin-like structure as a precursor is known.
- hsa-miR-2682-3p gene or “hsa-miR-2682-3p” refers to the hsa-miR-2682-3p gene described in SEQ ID NO: 323 (miRBase Accession No. MIMAT0013518) and other species homologs or orthologs.
- the hsa-miR-2682-3p gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- hsa-miR-2682-3p “hsa-mir-2682” (miRBase Accession No. MI0012063, SEQ ID NO: 716) having a hairpin-like structure as a precursor is known.
- hsa-miR-3122 gene or “hsa-miR-3122” refers to the hsa-miR-3122 gene (miRBase Accession No. MIMAT0014984) described in SEQ ID NO: 324 or other species. Homologs or orthologs are included.
- the hsa-miR-3122 gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- hsa-miR-3122 “hsa-mir-3122” (miRBase Accession No. MI0014138, SEQ ID NO: 717) having a hairpin-like structure as a precursor is known.
- hsa-miR-3151-5p gene or “hsa-miR-3151-5p” refers to the hsa-miR-3151-5p gene described in SEQ ID NO: 325 (miRBase Accession No. MIMAT0015024) and other species homologues or orthologues are included.
- the hsa-miR-3151-5p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “hsa-miR-3151-5p” is known as “hsa-mir-3151” (miRBase Accession No. MI0014178, SEQ ID NO: 661) having a hairpin-like structure as a precursor.
- hsa-miR-3175 gene or “hsa-miR-3175” refers to the hsa-miR-3175 gene (miRBase Accession No. MIMAT0015052) described in SEQ ID NO: 326 or other biological species. Homologs or orthologs are included.
- the hsa-miR-3175 gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- hsa-miR-3175 is known as “hsa-mir-3175” (miRBase Accession No. MI0014209, SEQ ID NO: 718) having a hairpin-like structure as a precursor.
- hsa-miR-4323 gene or “hsa-miR-4323” refers to the hsa-miR-4323 gene (miRBase Accession No. MIMAT0016875) described in SEQ ID NO: 327 or other biological species. Homologs or orthologs are included. The hsa-miR-4323 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. In addition, “hsa-miR-4323” is known as “hsa-mir-4323” (miRBase Accession No. MI0015853, SEQ ID NO: 719) having a hairpin-like structure as a precursor.
- hsa-miR-4326 gene or “hsa-miR-4326” refers to the hsa-miR-4326 gene (miRBase Accession No. MIMAT0016888) described in SEQ ID NO: 328 or other biological species. Homologs or orthologs are included. The hsa-miR-4326 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-4326”, “hsa-mir-4326” (miRBase Accession No. MI0015866, SEQ ID NO: 720) having a hairpin-like structure as a precursor is known.
- hsa-miR-4284 gene or “hsa-miR-4284” refers to the hsa-miR-4284 gene (miRBase Accession No. MIMAT0016915) described in SEQ ID NO: 329 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4284 gene was obtained from Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192.
- hsa-mir-4284 (miRBase Accession No. MI0015893, SEQ ID NO: 721) having a hairpin-like structure as a precursor is known.
- hsa-miR-3605-3p gene or “hsa-miR-3605-3p” refers to the hsa-miR-3605-3p gene described in SEQ ID NO: 330 (miRBase Accession No. MIMAT0017982) and other species homologues or orthologues are included.
- the hsa-miR-3605-3p gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- hsa-miR-3605-3p “hsa-mir-3605” (miRBase Accession No. MI0015995, SEQ ID NO: 722) having a hairpin-like structure as a precursor is known.
- hsa-miR-3622b-5p gene or “hsa-miR-3622b-5p” refers to the hsa-miR-3622b-5p gene described in SEQ ID NO: 331 (miRBase Accession No. 1). MIMAT0018005) and other species homologs or orthologs.
- the hsa-miR-3622b-5p gene was obtained from Witten D et al., 2010, BMC Biol. , 8, 58.
- “hsa-miR-3622b-5p” is known as “hsa-mir-3622b” (miRBase Accession No. MI0016014, SEQ ID NO: 723) having a hairpin-like structure as a precursor.
- hsa-miR-3646 gene or “hsa-miR-3646” refers to the hsa-miR-3646 gene (miRBase Accession No. MIMAT0018065) described in SEQ ID NO: 332 or other biological species. Homologs or orthologs are included.
- the hsa-miR-3646 gene is described in Meiri E et al., 2010, Nucleic Acids Res. 38, 6234-6246.
- hsa-miR-3646 is known as “hsa-mir-3646” (miRBase Accession No. MI0016046, SEQ ID NO: 724) having a hairpin-like structure as a precursor.
- hsa-miR-3158-5p gene or “hsa-miR-3158-5p” refers to the hsa-miR-3158-5p gene (miRBase Accession No. MIMAT0019211) and other species homologues or orthologues are included.
- the hsa-miR-3158-5p gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- “Hsa-miR-3158-5p” has a hairpin-like structure as a precursor thereof, “hsa-mir-3158-1, hsa-mir-3158-2” (miRBase Accession No. MI0014186, MI0014187, SEQ ID NO: 725,726) is known.
- hsa-miR-4722-3p gene or “hsa-miR-4722-3p” refers to the hsa-miR-4722-3p gene described in SEQ ID NO: 334 (miRBase Accession No. MIMAT0019837) and other species homologs or orthologs.
- the hsa-miR-4722-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4722-3p “hsa-mir-4722” (miRBase Accession No. MI0017357, SEQ ID NO: 727) having a hairpin-like structure as a precursor is known.
- hsa-miR-4728-3p gene or “hsa-miR-4728-3p” refers to the hsa-miR-4728-3p gene described in SEQ ID NO: 335 (miRBase Accession No. MIMAT0019850) and other species homologs or orthologs.
- the hsa-miR-4728-3p gene is described in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “hsa-miR-4728-3p” is known as “hsa-mir-4728” (miRBase Accession No. MI0017365, SEQ ID NO: 393) having a hairpin-like structure as a precursor.
- hsa-miR-4747-3p gene or “hsa-miR-4747-3p” refers to the hsa-miR-4747-3p gene described in SEQ ID NO: 336 (miRBase Accession No. MIMAT0019883) and other species homologs or orthologs.
- the hsa-miR-4747-3p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- hsa-miR-4747-3p “hsa-mir-4747” (miRBase Accession No. MI0017386, SEQ ID NO: 728) having a hairpin-like structure as a precursor is known.
- hsa-miR-4436b-5p gene or “hsa-miR-4436b-5p” refers to the hsa-miR-4436b-5p gene described in SEQ ID NO: 337 (miRBase Accession No. MIMAT0019940) and other species homologs or orthologs.
- the hsa-miR-4436b-5p gene is disclosed in Persson H et al., 2011, Cancer Res. 71, 78-86.
- “Hsa-miR-4436b-5p” has a hairpin-like structure as its precursor, “hsa-mir-4436b-1, hsa-mir-4436b-2” (miRBase Accession No. MI0017425, MI0019110, SEQ ID NO: 729, 730).
- hsa-miR-5196-3p gene or “hsa-miR-5196-3p” refers to the hsa-miR-5196-3p gene described in SEQ ID NO: 338 (miRBase Accession No. MIMAT0021129) and other species homologues or orthologues are included.
- the hsa-miR-5196-3p gene was obtained from Schotte D et al., 2011, Leukemia. 25, 1389-1399.
- hsa-miR-5196-3p “hsa-mir-5196” (miRBase Accession No. MI0018175, SEQ ID NO: 731) having a hairpin-like structure as a precursor is known.
- hsa-miR-5589-5p gene or “hsa-miR-5589-5p” refers to the hsa-miR-5589-5p gene described in SEQ ID NO: 339 (miRBase Accession No. MIMAT0022297) and other species homologs or orthologs.
- the hsa-miR-5589-5p gene was found in Friedlander MR et al., 2012, Nucleic Acids Res. 40, 37-52.
- “hsa-miR-5589-5p” is known as “hsa-mir-5589” (miRBase Accession No. MI0019148, SEQ ID NO: 732) having a hairpin-like structure as a precursor.
- hsa-miR-345-3p gene or “hsa-miR-345-3p” refers to the hsa-miR-345-3p gene described in SEQ ID NO: 340 (miRBase Accession No. MIMAT0022698) and other species homologs or orthologs.
- the hsa-miR-345-3p gene was found in Kim J et al., 2004, Proc Natl Acad Sci USA. 101, 360-365.
- “hsa-miR-345-3p” is known as “hsa-mir-345” (miRBase Accession No. MI000025, SEQ ID NO: 615) having a hairpin-like structure as a precursor.
- hsa-miR-642b-5p gene or “hsa-miR-642b-5p” refers to the hsa-miR-642b-5p gene described in SEQ ID NO: 341 (miRBase Accession No. MIMAT0022736) and other species homologues or orthologues are included.
- the hsa-miR-642b-5p gene was obtained from Witten D et al., 2010, BMC Biol. , 8, 58.
- “hsa-miR-642b-5p” is known as “hsa-mir-642b” (miRBase Accession No. MI0016685, SEQ ID NO: 733) having a hairpin-like structure as a precursor.
- hsa-miR-6716-3p gene or “hsa-miR-6716-3p” refers to the hsa-miR-6716-3p gene described in SEQ ID NO: 342 (miRBase Accession No. MIMAT0025845) and other species homologues or orthologues are included.
- the hsa-miR-6716-3p gene is described in Li Y et al., 2012, Gene. 497, 330-335.
- hsa-miR-6716-3p “hsa-mir-6716” (miRBase Accession No. MI0022550, SEQ ID NO: 734) having a hairpin-like structure as a precursor is known.
- hsa-miR-6511b-3p gene or “hsa-miR-6511b-3p” refers to the hsa-miR-6511b-3p gene described in SEQ ID NO: 343 (miRBase Accession No. MIMAT0025848) and other species homologs or orthologs.
- the hsa-miR-6511b-3p gene is disclosed in Li Y et al., 2012, Gene. 497, 330-335.
- “Hsa-miR-6511b-3p” has a hairpin-like structure as its precursor, “hsa-mir-6651b-1, hsa-mir-6511b-2” (miRBase Accession No. MI0022552, MI0023431, SEQ ID NO: 735, 736).
- hsa-miR-208a-5p gene or “hsa-miR-208a-5p” refers to the hsa-miR-208a-5p gene described in SEQ ID NO: 344 (miRBase Accession No. MIMAT0026474) and other species homologues or orthologues are included.
- the hsa-miR-208a-5p gene was obtained from Lagos-Quintana M et al., 2003, RNA. 9, 175-179.
- “hsa-miR-208a-5p” “hsa-mir-208a” (miRBase Accession No. MI000000251, SEQ ID NO: 737) having a hairpin-like structure as a precursor is known.
- hsa-miR-6726-3p gene or “hsa-miR-6726-3p” refers to the hsa-miR-6726-3p gene described in SEQ ID NO: 345 (miRBase Accession No. MIMAT0027354) and other species homologs or orthologs.
- the hsa-miR-6726-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6726-3p “hsa-mir-6726” (miRBase Accession No. MI0022571, SEQ ID NO: 600) having a hairpin-like structure as a precursor is known.
- hsa-miR-6744-5p gene or “hsa-miR-6744-5p” refers to the hsa-miR-6744-5p gene described in SEQ ID NO: 346 (miRBase Accession No. MIMAT0027389) and other species homologues or orthologues are included.
- the hsa-miR-6744-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6744-5p “hsa-mir-6744” (miRBase Accession No. MI0022589, SEQ ID NO: 738) having a hairpin-like structure as a precursor is known.
- hsa-miR-6787-3p gene or “hsa-miR-6787-3p” refers to the hsa-miR-6682-3p gene (miRBase Accession No. MIMAT0027465) and other species homologues or orthologues are included.
- the hsa-miR-6882-3p gene was obtained from Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6882-3p” is known as “hsa-mir-6782” (miRBase Accession No. MI0022627, SEQ ID NO: 739) having a hairpin-like structure as a precursor.
- hsa-miR-6789-3p gene or “hsa-miR-6789-3p” refers to the hsa-miR-6789-3p gene described in SEQ ID NO: 348 (miRBase Accession No. MIMAT0027479) and other species homologs or orthologs.
- the hsa-miR-6789-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6789-3p” is known as “hsa-mir-6789” (miRBase Accession No. MI0022634, SEQ ID NO: 740) having a hairpin-like structure as a precursor.
- hsa-miR-6797-3p gene or “hsa-miR-6797-3p” refers to the hsa-miR-6797-3p gene described in SEQ ID NO: 349 (miRBase Accession No. MIMAT0027495) and other species homologs or orthologs.
- the hsa-miR-6797-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6797-3p” is known as “hsa-mir-6797” (miRBase Accession No. MI0022642, SEQ ID NO: 741) having a hairpin-like structure as a precursor.
- hsa-miR-6800-3p gene or “hsa-miR-6800-3p” refers to the hsa-miR-6800-3p gene described in SEQ ID NO: 350 (miRBase Accession No. MIMAT0027501) and other species homologues or orthologues are included.
- the hsa-miR-6800-3p gene was found in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6800-3p” is known as “hsa-mir-6800” (miRBase Accession No. MI0022645, SEQ ID NO: 491) having a hairpin-like structure as a precursor.
- hsa-miR-6806-5p gene or “hsa-miR-6806-5p” refers to the hsa-miR-6806-5p gene described in SEQ ID NO: 351 (miRBase Accession No. 5). MIMAT0027512) and other species homologues or orthologues are included.
- the hsa-miR-6806-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6806-5p” is known as “hsa-mir-6806” (miRBase Accession No. MI0022651, SEQ ID NO: 742) having a hairpin-like structure as a precursor.
- hsa-miR-6824-3p gene or “hsa-miR-6824-3p” refers to the hsa-miR-6824-3p gene described in SEQ ID NO: 352 (miRBase Accession No. MIMAT0027549) and other species homologues or orthologues are included.
- the hsa-miR-6824-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6824-3p “hsa-mir-6824” (miRBase Accession No. MI0022669, SEQ ID NO: 743) having a hairpin-like structure as a precursor is known.
- hsa-miR-6837-5p gene or “hsa-miR-6837-5p” refers to the hsa-miR-6837-5p gene described in SEQ ID NO: 353 (miRBase Accession No. MIMAT0027576) and other species homologs or orthologs.
- the hsa-miR-6837-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6837-5p “hsa-mir-6683” (miRBase Accession No. MI0022683, SEQ ID NO: 744) having a hairpin-like structure as a precursor is known.
- hsa-miR-6864-3p gene or “hsa-miR-6846-3p” refers to the hsa-miR-6846-3p gene (miRBase Accession No. 5) described in SEQ ID NO: 354. MIMAT0027593) and other species homologs or orthologs.
- the hsa-miR-6864-3p gene was obtained from Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6846-3p” is known as “hsa-mir-6846” (miRBase Accession No. MI0022692, SEQ ID NO: 745) having a hairpin-like structure as a precursor.
- hsa-miR-6858-3p gene or “hsa-miR-6858-3p” refers to the hsa-miR-6858-3p gene described in SEQ ID NO: 355 (miRBase Accession No. MIMAT0027617) and other species homologues or orthologues are included.
- the hsa-miR-6858-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6858-3p” is known as “hsa-mir-6858” (miRBase Accession No. MI0022704, SEQ ID NO: 746) having a hairpin-like structure as a precursor.
- hsa-miR-6859-3p gene or “hsa-miR-6859-3p” refers to the hsa-miR-6859-3p gene described in SEQ ID NO: 356 (miRBase Accession No. MIMAT0027619) and other species homologues or orthologues are included.
- the hsa-miR-6859-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “Hsa-miR-6858-3p” has a hairpin-like structure as its precursor, “hsa-mir-6859-1, hsa-mir-6856-2, hsa-mir-6659-3, hsa-mir”.
- -6859-4 "(miRBBase Accession No. MI0022705, MI0026420, MI0026421, MI0031521, SEQ ID NOs: 747, 748, 749, 750) are known.
- hsa-miR-6861-3p gene or “hsa-miR-6861-3p” refers to the hsa-miR-6861-3p gene described in SEQ ID NO: 357 (miRBase Accession No. MIMAT0027624) and other species homologs or orthologs.
- the hsa-miR-6861-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6861-3p “hsa-mir-6861” (miRBase Accession No. MI0022708, SEQ ID NO: 596) having a hairpin-like structure as a precursor is known.
- hsa-miR-6880-3p gene or “hsa-miR-6880-3p” refers to the hsa-miR-6880-3p gene described in SEQ ID NO: 358 (miRBase Accession No. MIMAT0027661) and other species homologues or orthologues are included.
- the hsa-miR-6880-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6880-3p “hsa-mir-6880” (miRBase Accession No. MI0022727, SEQ ID NO: 751) having a hairpin-like structure as a precursor is known.
- hsa-miR-7111-3p gene or “hsa-miR-7111-3p” refers to the hsa-miR-7111-3p gene described in SEQ ID NO: 359 (miRBase Accession No. MIMAT0028120) and other species homologs or orthologs.
- the hsa-miR-7111-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-7111-3p “hsa-mir-7111” (miRBase Accession No. MI0022962, SEQ ID NO: 752) having a hairpin-like structure as a precursor is known.
- hsa-miR-7152-5p gene or “hsa-miR-7152-5p” refers to the hsa-miR-7152-5p gene described in SEQ ID NO: 360 (miRBase Accession No. MIMAT0028214) and other species homologues or orthologues are included.
- the hsa-miR-7152-5p gene is described in Meunier J et al., 2013, Genome Res. 23, 34-45.
- “hsa-miR-7152-5p” is known as “hsa-mir-7152” (miRBase Accession No. MI0023612, SEQ ID NO: 753) having a hairpin-like structure as a precursor.
- hsa-miR-642a-5p gene or “hsa-miR-642a-5p” refers to the hsa-miR-642a-5p gene described in SEQ ID NO: 361 (miRBase Accession No. MIMAT0003312) and other species homologs or orthologs.
- the hsa-miR-642a-5p gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci US A. 103, 3687-3692.
- “hsa-miR-642a-5p” is known as “hsa-mir-642a” (miRBase Accession No. MI0003657, SEQ ID NO: 754) having a hairpin-like structure as a precursor.
- hsa-miR-657 gene or “hsa-miR-657” refers to the hsa-miR-657 gene (miRBase Accession No. MIMAT0003335) described in SEQ ID NO: 362 or other biological species. Homologs or orthologs are included.
- the hsa-miR-657 gene was obtained from Cummins JM et al., 2006, Proc Natl Acad Sci USA. 103, 3687-3692.
- hsa-miR-657 “hsa-mir-657” (miRBase Accession No. MI0003681, SEQ ID NO: 755) having a hairpin-like structure as a precursor is known.
- hsa-miR-1236-3p gene or “hsa-miR-1236-3p” refers to the hsa-miR-1236-3p gene described in SEQ ID NO: 363 (miRBase Accession No. MIMAT0005591) and other species homologues or orthologues are included.
- the hsa-miR-1236-3p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- “hsa-miR-1236-3p” is known as “hsa-mir-1236” (miRBase Accession No. MI0006326, SEQ ID NO: 756) having a hairpin-like structure as a precursor.
- hsa-miR-764 gene or “hsa-miR-764” refers to the hsa-miR-764 gene (miRBase Accession No. MIMAT0010367) described in SEQ ID NO: 364 or other biological species. Homologs or orthologs are included.
- the hsa-miR-764 gene was obtained from Berezkov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-miR-764 “hsa-mir-764” (miRBase Accession No. MI0003944, SEQ ID NO: 757) having a hairpin-like structure as a precursor is known.
- hsa-miR-4314 gene or “hsa-miR-4314” refers to the hsa-miR-4314 gene (miRBase Accession No. MIMAT0016868) described in SEQ ID NO: 365 and other biological species. Homologs or orthologs are included. The hsa-miR-4314 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. As for “hsa-miR-4314”, “hsa-mir-4314” (miRBase Accession No. MI0015846, SEQ ID NO: 758) having a hairpin-like structure as a precursor is known.
- hsa-miR-3675-3p gene or “hsa-miR-3675-3p” refers to the hsa-miR-3675-3p gene described in SEQ ID NO: 366 (miRBase Accession No. MIMAT0018099) and other species homologs or orthologs.
- the hsa-miR-3675-3p gene was obtained from Vaz C et al., 2010, BMC Genomics. 11 and 288.
- “hsa-miR-3675-3p” is known as “hsa-mir-3675” (miRBase Accession No. MI0016076, SEQ ID NO: 759) having a hairpin-like structure as a precursor.
- hsa-miR-5703 gene or “hsa-miR-5703” refers to the hsa-miR-5703 gene (miRBase Accession No. MIMAT0022496) described in SEQ ID NO: 367 or other biological species. Homologs or orthologs are included.
- the hsa-miR-5703 gene was obtained from Watahiki A et al., 2011, PLoS One. 6, Volume 24, e24950.
- hsa-miR-5703 “hsa-mir-5703” (miRBase Accession No. MI0019310, SEQ ID NO: 760) having a hairpin-like structure as a precursor is known.
- hsa-miR-3191-5p gene or “hsa-miR-3191-5p” refers to the hsa-miR-3191-5p gene described in SEQ ID NO: 368 (miRBase Accession No. MIMAT0022732) and other species homologues or orthologues are included.
- the hsa-miR-3191-5p gene was obtained from Stark MS et al., 2010, PLoS One. No. 5, vol. E9685.
- “hsa-miR-3191-5p” is known as “hsa-mir-3191” (miRBase Accession No. MI0014236, SEQ ID NO: 761) having a hairpin-like structure as a precursor.
- hsa-miR-6511a-3p gene or “hsa-miR-6511a-3p” refers to the hsa-miR-6511a-3p gene described in SEQ ID NO: 369 (miRBase Accession No. MIMAT0025479) and other species homologs or orthologs.
- the hsa-miR-6511a-3p gene was obtained from Joyce CE et al., 2011, Hum Mol Genet. 20, Vol. 4025-4040.
- “hsa-miR-6511a-3p” is known as “hsa-mir-6511a-1” (miRBase Accession No. MI0022223, SEQ ID NO: 445) having a hairpin-like structure as a precursor.
- hsa-miR-6809-3p gene or “hsa-miR-6809-3p” refers to the hsa-miR-6809-3p gene described in SEQ ID NO: 370 (miRBase Accession No. MIMAT0027519) and other species homologues or orthologues are included.
- the hsa-miR-6809-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6809-3p” is known as “hsa-mir-6809” (miRBase Accession No. MI0022654, SEQ ID NO: 762) having a hairpin-like structure as a precursor.
- hsa-miR-6815-5p gene or “hsa-miR-6815-5p” refers to the hsa-miR-6815-5p gene described in SEQ ID NO: 371 (miRBase Accession No. MIMAT0027530) and other species homologues or orthologues are included.
- the hsa-miR-6815-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6815-5p” is known as “hsa-mir-6815” (miRBase Accession No. MI0022660, SEQ ID NO: 763) having a hairpin-like structure as a precursor.
- hsa-miR-6857-3p gene or “hsa-miR-6857-3p” refers to the hsa-miR-6857-3p gene described in SEQ ID NO: 372 (miRBase Accession No. MIMAT0027615) and other species homologs or orthologs.
- the hsa-miR-6857-3p gene is disclosed in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- hsa-miR-6857-3p “hsa-mir-6857” (miRBase Accession No. MI0022703, SEQ ID NO: 764) having a hairpin-like structure as a precursor is known.
- hsa-miR-6878-3p gene or “hsa-miR-6878-3p” refers to the hsa-miR-6878-3p gene described in SEQ ID NO: 373 (miRBase Accession No. MIMAT0027657) and other species homologs or orthologs.
- the hsa-miR-6878-3p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6878-3p” is known as “hsa-mir-6878” (miRBase Accession No. MI0022725, SEQ ID NO: 765) having a hairpin-like structure as a precursor.
- hsa-miR-371a-5p gene or “hsa-miR-371a-5p” refer to the hsa-miR-371a-5p gene described in SEQ ID NO: 374 (miRBase Accession No. MIMAT0004687) and other species homologues or orthologues are included.
- the hsa-miR-371a-5p gene is described in Suh MR et al., 2004, Dev Biol. 270, 488-498.
- hsa-miR-371a-5p “hsa-mir-371a” (miRBase Accession No. MI000079, SEQ ID NO: 766) having a hairpin-like structure as a precursor is known.
- hsa-miR-766-3p gene or “hsa-miR-766-3p” refers to the hsa-miR-766-3p gene described in SEQ ID NO: 375 (miRBase Accession No. MIMAT0003888) and other species homologues or orthologues are included.
- the hsa-miR-766-3p gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-miR-766-3p “hsa-mir-766” (miRBase Accession No. MI0003836, SEQ ID NO: 767) having a hairpin-like structure as a precursor is known.
- hsa-miR-1229-3p gene or “hsa-miR-1229-3p” refers to the hsa-miR-1229-3p gene described in SEQ ID NO: 376 (miRBase Accession No. MIMAT0005584) and other species homologs or orthologs.
- the hsa-miR-1229-3p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- “hsa-miR-1229-3p” is known as “hsa-mir-1229” (miRBase Accession No. MI0006319, SEQ ID NO: 768) having a hairpin-like structure as a precursor.
- hsa-miR-1306-5p gene or “hsa-miR-1306-5p” refers to the hsa-miR-1306-5p gene described in SEQ ID NO: 377 (miRBase Accession No. MIMAT0022726) and other species homologs or orthologs.
- the hsa-miR-1306-5p gene is described in Morin RD et al., 2008, Genome Res. 18, 610-621.
- hsa-miR-1306-5p “hsa-mir-1306” (miRBase Accession No. MI0006443, SEQ ID NO: 769) having a hairpin-like structure as a precursor is known.
- hsa-miR-210-5p gene or “hsa-miR-210-5p” refers to the hsa-miR-210-5p gene described in SEQ ID NO: 378 (miRBase Accession No. MIMAT0026475) and other species homologs or orthologs.
- the hsa-miR-210-5p gene is described in Lim LP et al., 2003, Science. 299, 1540.
- hsa-mir-210 miRBase Accession No. MI00000028, SEQ ID NO: 770 having a hairpin-like structure as a precursor is known.
- hsa-miR-198 gene or “hsa-miR-198” refers to the hsa-miR-198 gene (miRBase Accession No. MIMAT000028) described in SEQ ID NO: 379 or other species. Homologs or orthologs are included.
- the hsa-miR-198 gene was obtained from Lagos-Quintana M et al., 2003, RNA. 9, 175-179.
- hsa-miR-198 “hsa-mir-198” (miRBase Accession No. MI0000240, SEQ ID NO: 771) having a hairpin-like structure as a precursor is known.
- hsa-miR-485-3p gene or “hsa-miR-485-3p” refers to the hsa-miR-485-3p gene described in SEQ ID NO: 380 (miRBase Accession No. MIMAT0002176) and other species homologues or orthologues are included.
- the hsa-miR-485-3p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-485-3p” is known as “hsa-mir-485” (miRBase Accession No. MI0002469, SEQ ID NO: 772) having a hairpin-like structure as a precursor.
- hsa-miR-668-3p gene or “hsa-miR-668-3p” refers to the hsa-miR-668-3p gene described in SEQ ID NO: 381 (miRBase Accession No. MIMAT0003881) and other species homologues or orthologues are included.
- the hsa-miR-668-3p gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-miR-668-3p “hsa-mir-668” (miRBase Accession No. MI0003761, SEQ ID NO: 773) having a hairpin-like structure as a precursor is known.
- hsa-miR-532-3p gene or “hsa-miR-532-3p” refers to the hsa-miR-532-3p gene described in SEQ ID NO: 382 (miRBase Accession No. MIMAT0004780) and other species homologs or orthologs.
- the hsa-miR-532-3p gene is described in Lagos-Quintana M et al., 2001, Science. 294, 853-858.
- “hsa-miR-532-3p” is known as “hsa-mir-532” (miRBase Accession No. MI0003205, SEQ ID NO: 626) having a hairpin-like structure as a precursor.
- hsa-miR-877-3p gene or “hsa-miR-877-3p” refers to the hsa-miR-877-3p gene described in SEQ ID NO: 383 (miRBase Accession No. MIMAT0004950) and other species homologs or orthologs.
- the hsa-miR-877-3p gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- hsa-miR-877-3p is known as “hsa-mir-877” (miRBase Accession No. MI0005561, SEQ ID NO: 774) having a hairpin-like structure as a precursor.
- hsa-miR-1238-3p gene or “hsa-miR-1238-3p” refers to the hsa-miR-1238-3p gene described in SEQ ID NO: 384 (miRBase Accession No. MIMAT0005593) and other species homologues or orthologues are included.
- the hsa-miR-1238-3p gene was obtained from Berezikov E et al., 2007, Mol Cell. 28, 328-336.
- “hsa-miR-1238-3p” is known as “hsa-mir-1238” (miRBase Accession No. MI0006328, SEQ ID NO: 775) having a hairpin-like structure as a precursor.
- hsa-miR-3130-5p gene or “hsa-miR-3130-5p” refers to the hsa-miR-3130-5p gene described in SEQ ID NO: 385 (miRBase Accession No. MIMAT0014995) and other species homologs or orthologs.
- the hsa-miR-3130-5p gene was obtained from Creighton CJ et al., 2010, PLoS One. 5, Vol. 5, e9637.
- “Hsa-miR-3130-5p” has a hairpin-like structure as its precursor, “hsa-mir-3130-1, hsa-mir-3130-2” (miRBase Accession No. MI0014147, MI0014148, SEQ ID NO: 776,777) are known.
- hsa-miR-4298 gene or “hsa-miR-4298” refers to the hsa-miR-4298 gene (miRBase Accession No. MIMAT0016852) described in SEQ ID NO: 386 or other biological species. Homologs or orthologs are included. The hsa-miR-4298 gene was found in Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192. Also, “hsa-miR-4298” is known as “hsa-mir-4298” (miRBase Accession No. MI0015830, SEQ ID NO: 778) having a hairpin-like structure as a precursor.
- hsa-miR-4290 gene or “hsa-miR-4290” refers to the hsa-miR-4290 gene (miRBase Accession No. MIMAT0016921) described in SEQ ID NO: 387 and other biological species. Homologs or orthologs are included.
- the hsa-miR-4290 gene was obtained from Goff LA et al., 2009, PLoS One. 4, Volume 4, e7192.
- “hsa-miR-4290” is known as “hsa-mir-4290” (miRBase Accession No. MI0015899, SEQ ID NO: 779) having a hairpin-like structure as a precursor.
- hsa-miR-3943 gene or “hsa-miR-3943” refers to the hsa-miR-3943 gene (miRBase Accession No. MIMAT0018359) described in SEQ ID NO: 388 or other biological species. Homologs or orthologs are included. The hsa-miR-3943 gene was found in Liao JY et al., 2010, PLoS One. 5, Vol. 5, e10563. Also, “hsa-miR-3943” is known as “hsa-mir-3943” (miRBase Accession No. MI0016600, SEQ ID NO: 780) having a hairpin-like structure as a precursor.
- hsa-miR-346 gene or “hsa-miR-346” refers to the hsa-miR-346 gene (miRBase Accession No. MIMAT000003) described in SEQ ID NO: 389 or other biological species. Homologs or orthologs are included.
- the hsa-miR-346 gene was found in Kim J et al., 2004, Proc Natl Acad Sci US A. 101, 360-365.
- hsa-mir-346 (miRBase Accession No. MI000026, SEQ ID NO: 781) having a hairpin-like structure as a precursor is known.
- hsa-miR-767-3p gene or “hsa-miR-767-3p” refers to the hsa-miR-767-3p gene described in SEQ ID NO: 390 (miRBase Accession No. MIMAT0003883) and other species homologs or orthologs are included.
- the hsa-miR-767-3p gene was obtained from Berezikov E et al., 2006, Genome Res. 16, Vol. 1629-1298.
- “Hsa-miR-767-3p” is known as “hsa-mir-767” (miRBase Accession No. MI0003763, SEQ ID NO: 782) having a hairpin-like structure as a precursor.
- hsa-miR-6765-3p gene or “hsa-miR-6765-3p” refers to the hsa-miR-6765-3p gene described in SEQ ID NO: 1315 (miRBaseAccession No. MIMAT0027431) And other species homologs or orthologs.
- the hsa-miR-6765-3p gene can be obtained by the method described in LadewigE et al., 2012, GenomeRes, 22, p1634-1645.
- hsa-mir-6765 miRBaseAccession No. MI0022610, SEQ ID NO: 490 having a hairpin-like structure as a precursor is known.
- hsa-miR-6784-5p gene or “hsa-miR-6784-5p” refer to the hsa-miR-6784-5p gene described in SEQ ID NO: 1316 (miRBaseAccessionNo.MIMAT0027468) And other species homologs or orthologs.
- the hsa-miR-6784-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “hsa-miR-6784-5p” “hsa-mir-6784” (miRBaseAccession No. MI0022629, SEQ ID NO: 1357) having a hairpin-like structure as a precursor is known.
- hsa-miR-6778-5p gene or “hsa-miR-6778-5p” refers to the hsa-miR-6778-5p gene described in SEQ ID NO: 1317 (miRBaseAccessionNo. MIMAT0027456). And other species homologs or orthologs.
- the hsa-miR-6778-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645.
- “hsa-miR-6778-5p” is known as “hsa-mir-6778” (miRBaseAccession No. MI0022623, SEQ ID NO: 1358) having a hairpin-like structure as a precursor.
- hsa-miR-6875-5p gene or “hsa-miR-6875-5p” refers to the hsa-miR-6875-5p gene set forth in SEQ ID NO: 1318 (miRBaseAccessionNo. MIMAT0027650). And other species homologs or orthologs.
- the hsa-miR-6875-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, Vol. 22, p1634-1645.
- “hsa-miR-6875-5p” “hsa-mir-6875” (miRBaseAccession No. MI0022722, SEQ ID NO: 1359) having a hairpin-like structure as a precursor is known.
- hsa-miR-4534 gene or “hsa-miR-4534” refers to the hsa-miR-4534 gene (miRBaseAccession No. MIMAT0019073) described in SEQ ID NO: 1319 or other species homolog Orthologs and the like are included.
- the hsa-miR-4534 gene can be obtained by the method described in JimDD et al., 2010, Blood, 116, e118-e127.
- hsa-mir-4534 miRBaseAccession No. MI0016901, SEQ ID NO: 1360 having a hairpin-like structure as a precursor is known.
- hsa-miR-4721 gene or “hsa-miR-4721” refers to the hsa-miR-4721 gene (miRBaseAccession No. MIMAT0019835) described in SEQ ID NO: 1320 or other species homolog or Orthologs and the like are included.
- the hsa-miR-4721 gene can be obtained by the method described in PerssonH et al., 2011, Cancer Res, 71, p78-86.
- “hsa-miR-4721” “hsa-mir-4721” (miRBaseAccession No. MI0017356, SEQ ID NO: 1361), which takes a hairpin-like structure as a precursor, is known.
- hsa-miR-6756-5p gene or “hsa-miR-6756-5p” refers to the hsa-miR-6756-5p gene described in SEQ ID NO: 1321 (miRBaseAccessionNo.MIMAT0027412). And other species homologs or orthologs.
- the hsa-miR-6756-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “hsa-miR-6756-5p” is known as “hsa-mir-6756” (miRBaseAccession No. MI0022601, SEQ ID NO: 1362) having a hairpin-like structure as a precursor.
- hsa-miR-615-5p gene or “hsa-miR-615-5p” refers to the hsa-miR-615-5p gene described in SEQ ID NO: 1322 (miRBaseAccession No. MIMAT0004804). And other species homologs or orthologs.
- the hsa-miR-615-5p gene can be obtained by the method described in Cummins JM et al., 2006, ProcNatlAcadSciUSA, 103, p3687-3692.
- hsa-miR-615-5p “hsa-mir-615” (miRBaseAccession No. MI0003628, SEQ ID NO: 1363) having a hairpin-like structure as a precursor is known.
- hsa-miR-6727-5p gene or “hsa-miR-6727-5p” refers to the hsa-miR-6727-5p gene described in SEQ ID NO: 1323 (miRBaseAccessionNo.MIMAT0027355). And other species homologs or orthologs.
- the hsa-miR-6727-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “hsa-miR-6727-5p” “hsa-mir-6727” (miRBaseAccession No. MI0022572, SEQ ID NO: 1364) having a hairpin-like structure as a precursor is known.
- hsa-miR-687-5p gene or “hsa-miR-6687-5p” refers to the hsa-miR-6687-5p gene described in SEQ ID NO: 1324 (miRBaseAccessionNo.MIMAT0027674). And other species homologs or orthologs.
- the hsa-miR-6687-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “hsa-miR-687-5p” is known as “hsa-mir-6687” (miRBaseAccession No. MI0022734, SEQ ID NO: 1365) having a hairpin-like structure as a precursor.
- hsa-miR-8063 gene or “hsa-miR-8063” refers to the hsa-miR-8063 gene (miRBaseAccession No. MIMAT0030990) described in SEQ ID NO: 1325 or other species homolog or Orthologs and the like are included.
- the hsa-miR-8063 gene can be obtained by the method described in WangHJ et al., 2013, Shock, 39, p480-487.
- hsa-miR-8063 “hsa-mir-8063” (miRBaseAccession No. MI0025899, SEQ ID NO: 1366) having a hairpin-like structure as a precursor is known.
- hsa-miR-6880-5p gene or “hsa-miR-6880-5p” refers to the hsa-miR-6880-5p gene described in SEQ ID NO: 1326 (miRBaseAccessionNo.MIMAT0027660). And other species homologs or orthologs.
- the hsa-miR-6880-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645.
- “hsa-miR-6880-5p” is known as “hsa-mir-6880” (miRBaseAccession No. MI0022727, SEQ ID NO: 1367) having a hairpin-like structure as a precursor.
- hsa-miR-6805-3p gene or “hsa-miR-6805-3p” refers to the hsa-miR-6805-3p gene described in SEQ ID NO: 1327 (miRBaseAccession No. MIMAT0027511). And other species homologs or orthologs.
- the hsa-miR-6805-3p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645.
- “hsa-miR-6805-3p” is known as “hsa-mir-6805” (miRBaseAccession No. MI0022650, SEQ ID NO: 1368) having a hairpin-like structure as a precursor.
- hsa-miR-4726-5p gene or “hsa-miR-4726-5p” refers to the hsa-miR-4726-5p gene described in SEQ ID NO: 1328 (miRBaseAccession No. MIMAT0019845). And other species homologs or orthologs.
- the hsa-miR-4726-5p gene can be obtained by the method described in Personson H et al., 2011, Cancer Res, 71, p78-86.
- “hsa-miR-4726-5p” is known as “hsa-mir-4726” (miRBaseAccession No. MI0017363, SEQ ID NO: 1369) having a hairpin-like structure as a precursor.
- hsa-miR-4710 gene or “hsa-miR-4710” refers to the hsa-miR-4710 gene (miRBaseAccession No. MIMAT0019815) described in SEQ ID NO: 1329 or other species homolog Orthologs and the like are included.
- the hsa-miR-4710 gene can be obtained by the method described in PerssonH et al., 2011, Cancer Res, 71, p78-86.
- “hsa-miR-4710” “hsa-mir-4710” (miRBaseAccession No. MI0017344, SEQ ID NO: 1370), which has a hairpin-like structure as a precursor, is known.
- hsa-miR-7111-5p gene or “hsa-miR-7111-5p” refers to the hsa-miR-7111-5p gene described in SEQ ID NO: 1330 (miRBaseAccession No. MIMAT0028119). And other species homologs or orthologs.
- the hsa-miR-7111-5p gene can be obtained by the method described in Ladewig E et al., 2012, Genome Res, 22, p1634-1645.
- hsa-miR-7111-5p “hsa-mir-7111” (miRBaseAccession No. MI0022962, SEQ ID NO: 1371) having a hairpin-like structure as a precursor is known.
- hsa-miR-3619-3p gene or “hsa-miR-3619-3p” refers to the hsa-miR-3619-3p gene described in SEQ ID NO: 1331 (miRBaseAccession No. MIMAT0019219). And other species homologs or orthologs.
- the hsa-miR-3619-3p gene can be obtained by the method described in WittenD et al., 2010, BMC Biol, 8, p58.
- “hsa-miR-3619-3p” “hsa-mir-3619” (miRBaseAccession No. MI0016009, SEQ ID NO: 1372) having a hairpin-like structure as a precursor is known.
- hsa-miR-6695-5p gene or “hsa-miR-6695-5p” refers to the hsa-miR-6695-5p gene described in SEQ ID NO: 1332 (miRBaseAccessionNo. MIMAT0027490). And other species homologs or orthologs.
- the hsa-miR-6695-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “Hsa-miR-6695-5p” is known as “hsa-mir-6695” (miRBaseAccession No. MI0022640, SEQ ID NO: 1373) having a hairpin-like structure as a precursor.
- hsa-miR-1254 gene or “hsa-miR-1254” refers to the hsa-miR-1254 gene (miRBaseAccession No. MIMAT0005905) described in SEQ ID NO: 1333 or other species homolog or Orthologs and the like are included.
- the hsa-miR-1254 gene can be obtained by the method described in MorinRD et al., 2008, GenomeRes, 18, p610-621.
- “Hsa-miR-1254” has a hairpin-like structure as a precursor thereof, “hsa-mir-1254-1, hsa-mir-1254-2” (miRBaseAccession No. MI0006388, MI0016747, SEQ ID NOs: 1374, 1375). It has been known.
- hsa-miR-1233-5p gene or “hsa-miR-1233-5p” refers to the hsa-miR-1233-5p gene described in SEQ ID NO: 1334 (miRBaseAccession No. MIMAT0022943). And other species homologs or orthologs.
- the hsa-miR-1233-5p gene can be obtained by the method described in Berezikov E et al., 2007, Mol Cell, 28, p328-336.
- “hsa-miR-1233-5p” has “hsa-mir-1233-1, hsa-mir-1233-2” (miRBaseAccession No. MI0006323, MI0015973, SEQ ID NO: 1376, which takes a hairpin-like structure as a precursor thereof. 1377) is known.
- hsa-miR-6836-3p gene or “hsa-miR-6836-3p” refers to the hsa-miR-6636-3p gene set forth in SEQ ID NO: 1335 (miRBaseAccession No. MIMAT0027575). And other species homologs or orthologs.
- the hsa-miR-6683-3p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- hsa-miR-6836-3p “hsa-mir-6836” (miRBaseAccession No. MI0022682, SEQ ID NO: 1378) having a hairpin-like structure as a precursor is known.
- hsa-miR-6769a-5p gene or “hsa-miR-6769a-5p” refers to the hsa-miR-6769a-5p gene described in SEQ ID NO: 1336 (miRBaseAccession No. MIMAT0027438). And other species homologs or orthologs.
- the hsa-miR-6769a-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “hsa-miR-6769a-5p” is known as “hsa-mir-6769a” (miRBaseAccession No. MI0022614, SEQ ID NO: 1379) having a hairpin-like structure as a precursor.
- hsa-miR-4532 gene or “hsa-miR-4532” refers to the hsa-miR-4532 gene (miRBaseAccession No. MIMAT0019071) described in SEQ ID NO: 1337 or other species homolog Orthologs and the like are included.
- the hsa-miR-4532 gene can be obtained by the method described in JimDD et al., 2010, Blood, 116, e118-e127.
- hsa-mir-4532 miRBaseAccession No. MI0016899, SEQ ID NO: 1380 having a hairpin-like structure as a precursor is known.
- hsa-miR-365a-5p gene or “hsa-miR-365a-5p” refers to the hsa-miR-365a-5p gene described in SEQ ID NO: 1338 (miRBaseAccessionNo. MIMAT0009199). And other species homologs or orthologs.
- the hsa-miR-365a-5p gene can be obtained by the method described in XieX et al., 2005, Nature, 434, p338-345.
- hsa-mir-365a miRBaseAccession No. MI000067, SEQ ID NO: 1381 having a hairpin-like structure as a precursor is known.
- hsa-miR-1231 gene or “hsa-miR-1231” refers to the hsa-miR-1231 gene (miRBaseAccession No. MIMAT0005586) described in SEQ ID NO: 1339 or other species homolog Orthologs and the like are included.
- the hsa-miR-1231 gene can be obtained by the method described in Berezkov E et al., 2007, MolCell, 28, p328-336.
- “hsa-miR-1231” is known as “hsa-mir-1231” (miRBaseAccession No. MI0006321, SEQ ID NO: 1382) having a hairpin-like structure as a precursor.
- hsa-miR-1228-5p gene or “hsa-miR-1228-5p” refers to the hsa-miR-1228-5p gene described in SEQ ID NO: 1340 (miRBaseAccession No. MIMAT0005582). And other species homologs or orthologs.
- the hsa-miR-1228-5p gene can be obtained by the method described in Berezikov E et al., 2007, MolCell, 28, p328-336.
- “hsa-miR-1228-5p” is known as “hsa-mir-1228” (miRBaseAccession No. MI0006318, SEQ ID NO: 1383) having a hairpin-like structure as a precursor.
- hsa-miR-4430 gene or “hsa-miR-4430” refers to the hsa-miR-4430 gene (miRBaseAccession No. MIMAT0018945) described in SEQ ID NO: 1341, homologs of other species or Orthologs and the like are included.
- the hsa-miR-4430 gene can be obtained by the method described in JimDD et al., 2010, Blood, 116, e118-e127.
- hsa-mir-4430 (miRBaseAccession No. MI0016769, SEQ ID NO: 1384) having a hairpin-like structure as a precursor is known.
- hsa-miR-296-3p gene or “hsa-miR-296-3p” refers to the hsa-miR-296-3p gene described in SEQ ID NO: 1342 (miRBaseAccession No. MIMAT0004679). And other species homologs or orthologs.
- the hsa-miR-296-3p gene can be obtained by the method described in Houbaviy HB et al., 2003, DevCell, 5, p351-358.
- hsa-miR-296-3p “hsa-mir-296” (miRBaseAccession No. MI000047, SEQ ID NO: 1385), which has a hairpin-like structure as a precursor, is known.
- hsa-miR-1237-5p gene or “hsa-miR-1237-5p” refers to the hsa-miR-1237-5p gene described in SEQ ID NO: 1343 (miRBaseAccessionNo.MIMAT0022946). And other species homologs or orthologs.
- the hsa-miR-1237-5p gene can be obtained by the method described in Berezikov E et al., 2007, MolCell, 28, p328-336.
- hsa-mir-1237 miRBaseAccession No. MI0006327, SEQ ID NO: 1386
- hsa-miR-4466 gene or “hsa-miR-4466” refers to the hsa-miR-4466 gene (miRBaseAccession No. MIMAT0018993) described in SEQ ID NO: 1344 Orthologs and the like are included.
- the hsa-miR-4466 gene can be obtained by the method described in JimDD et al., 2010, Blood, 116, e118-e127.
- hsa-mir-4466 (miRBaseAccession No. MI0016817, SEQ ID NO: 1387) having a hairpin-like structure as a precursor is known.
- hsa-miR-6789-5p gene or “hsa-miR-6789-5p” refers to the hsa-miR-6789-5p gene described in SEQ ID NO: 1345 (miRBaseAccessionNo.MIMAT0027478). And other species homologs or orthologs.
- the hsa-miR-6789-5p gene is described in Ladewig E et al., 2012, Genome Res. No. 22, p1634-645.
- hsa-miR-6789-5p “hsa-mir-6789” (miRBaseAccession No. MI0022634, SEQ ID NO: 1388) having a hairpin-like structure as a precursor is known.
- hsa-miR-4632-5p gene or “hsa-miR-4632-5p” refers to the hsa-miR-4632-5p gene described in SEQ ID NO: 1346 (miRBaseAccession No. MIMAT0022977). And other species homologs or orthologs.
- the hsa-miR-4632-5p gene can be obtained by the method described in PerssonH et al., 2011, Cancer Res, 71, p78-86.
- “hsa-miR-4632-5p” is known as “hsa-mir-4632” (miRBaseAccession No. MI0017259, SEQ ID NO: 1389) having a hairpin-like structure as a precursor.
- hsa-miR-4745-5p gene or “hsa-miR-4745-5p” refer to the hsa-miR-4745-5p gene described in SEQ ID NO: 1347 (miRBaseAccession No. MIMAT0019878). And other species homologs or orthologs.
- the hsa-miR-4745-5p gene can be obtained by the method described in PerssonH et al., 2011, Cancer Res, 71, p78-86.
- “Hsa-miR-4745-5p” is known as “hsa-mir-4745” (miRBaseAccession No. MI0017384, SEQ ID NO: 1390) having a hairpin-like structure as a precursor.
- hsa-miR-4665-5p gene or “hsa-miR-4665-5p” refers to the hsa-miR-4665-5p gene set forth in SEQ ID NO: 1348 (miRBaseAccession No. MIMAT0019739). And other species homologs or orthologs.
- the hsa-miR-4665-5p gene can be obtained by the method described in PerssonH et al., 2011, Cancer Res, 71, p78-86.
- “hsa-miR-4665-5p” is known as “hsa-mir-4665” (miRBaseAccession No. MI0017295, SEQ ID NO: 1391), which has a hairpin-like structure as a precursor.
- hsa-miR-6807-5p gene or “hsa-miR-6807-5p” refers to the hsa-miR-6807-5p gene described in SEQ ID NO: 1349 (miRBaseAccession No. MIMAT0027514). And other species homologs or orthologs.
- the hsa-miR-6807-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “hsa-miR-6807-5p” is known as “hsa-mir-6807” (miRBaseAccession No. MI0022652, SEQ ID NO: 1392) having a hairpin-like structure as a precursor.
- hsa-miR-7114-5p gene or “hsa-miR-7114-5p” refers to the hsa-miR-7114-5p gene described in SEQ ID NO: 1350 (miRBaseAccessionNo.MIMAT0028125). And other species homologs or orthologs.
- the hsa-miR-7114-5p gene can be obtained by the method described in Ladewig E et al., 2012, GenomeRes, 22, p1634-1645.
- “hsa-miR-7114-5p” “hsa-mir-7114” (miRBaseAccession No. MI0022965, SEQ ID NO: 1393) having a hairpin-like structure as a precursor is known.
- hsa-miR-150-3p gene or “hsa-miR-150-3p” refers to the hsa-miR-150-3p gene described in SEQ ID NO: 1351 (miRBaseAccession No. MIMAT0004610). And other species homologs or orthologs.
- the hsa-miR-150-3p gene can be obtained by the method described in Lagos-QuintanaM et al., 2002, CurrBiol, 12, p735-739.
- “hsa-miR-150-3p” “hsa-mir-150” (miRBaseAccession No. MI0000479, SEQ ID NO: 1394) having a hairpin-like structure as a precursor is known.
- hsa-miR-423-5p gene or “hsa-miR-423-5p” refers to the hsa-miR-423-5p gene described in SEQ ID NO: 1352 (miRBaseAccessionNo.MIMAT0004748). And other species homologs or orthologs.
- the hsa-miR-423-5p gene can be obtained by the method described in Kasshima K et al., 2004, Biochem Biophys ResCommun, 322, p403-410.
- “hsa-miR-423-5p” “hsa-mir-423” (miRBaseAccession No. MI0001445, SEQ ID NO: 1395) having a hairpin-like structure as a precursor is known.
- hsa-miR-575 gene or “hsa-miR-575” refers to the hsa-miR-575 gene (miRBaseAccession No. MIMAT0003240) described in SEQ ID NO: 1353 or other species homolog Orthologs and the like are included.
- the hsa-miR-575 gene can be obtained by the method described in Cummins JM et al., 2006, ProcNatlAcadSciUSA, 103, p3687-3692.
- hsa-miR-575 “hsa-mir-575” (miRBaseAccession No. MI0003582, SEQ ID NO: 1396) having a hairpin-like structure as a precursor is known.
- hsa-miR-671-5p gene or “hsa-miR-671-5p” refers to the hsa-miR-671-5p gene described in SEQ ID NO: 1354 (miRBaseAccession No. MIMAT0003880). And other species homologs or orthologs.
- the hsa-miR-671-5p gene is described in Berezikov E et al., 2006, Genome Res. 16, p. 1299-1298.
- “hsa-miR-671-5p” is known as “hsa-mir-671” (miRBaseAccession No. MI0003760, SEQ ID NO: 1397), which has a hairpin-like structure as a precursor.
- hsa-miR-939-5p gene or “hsa-miR-939-5p” refers to the hsa-miR-939-5p gene described in SEQ ID NO: 1355 (miRBaseAccession No. MIMAT0004982). And other species homologs or orthologs.
- the hsa-miR-939-5p gene is described in LuiWO et al., 2007, Cancer Res. 67, p6031-6043.
- hsa-mir-939 miRBaseAccession No. MI0005761, SEQ ID NO: 1398) having a hairpin-like structure as a precursor is known.
- hsa-miR-3665 gene or “hsa-miR-3665” refers to the hsa-miR-3665 gene (miRBaseAccession No. MIMAT0018087) described in SEQ ID NO: 1356 or other species homolog or Orthologs and the like are included.
- the hsa-miR-3665 gene can be obtained by the method described in XieX et al., 2005, Nature, 434, p338-345.
- hsa-miR-3665 “hsa-mir-3665” (miRBaseAccession No. MI0016066, SEQ ID NO: 1399) having a hairpin-like structure as a precursor is known.
- hsa-miR-516a-5p gene or “hsa-miR-516a-5p” refers to the hsa-miR-516a-5p gene described in SEQ ID NO: 1435 (miRBase Accession No. 1). MIMAT0004770) and other species homologs or orthologs.
- the hsa-miR-516a-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-516a-5p” is known as “hsa-miR-516a-1” (miRBase Accession No. MI0003180, SEQ ID NO: 1454) having a hairpin-like structure as a precursor.
- hsa-miR-769-3p gene or “hsa-miR-769-3p” refers to the hsa-miR-769-3p gene (miRBase Accession No. 1) described in SEQ ID NO: 1436. MIMAT0003887) and other species homologues or orthologues are included.
- the hsa-miR-769-3p gene was obtained from Berezikov E et al., 2006, Genome Res. 16 can be obtained by the method described in 1289-1298.
- “hsa-miR-769-3p” is known as “hsa-miR-769-3p” (miRBase Accession No. MI0003834, SEQ ID NO: 1465) having a hairpin-like structure as a precursor.
- hsa-miR-3692-5p gene or “hsa-miR-3692-5p” refers to the hsa-miR-3692-5p gene (miRBase Accession No. 1) described in SEQ ID NO: 1437. MIMAT0018121) and other species homologues or orthologues are included.
- the hsa-miR-3692-5p gene is disclosed in Vaz C et al., 2010, BMC Genomics. , 11 and 288.
- “hsa-miR-3692-5p” is known as “hsa-miR-3692-5p” (miRBase Accession No. MI0016093, SEQ ID NO: 1456), which has a hairpin-like structure as a precursor.
- hsa-miR-3945 gene or “hsa-miR-3945” refers to the hsa-miR-3945 gene (miRBase Accession No. MIMAT0018361) described in SEQ ID NO: 1438 and other biological species. Homologs or orthologs are included.
- the hsa-miR-3945 gene was found in Liao JY et al., 2010, PLoS One. 5 and can be obtained by the method described in e10563.
- “hsa-miR-3945” “hsa-miR-3945” (miRBase Accession No. MI0016602, SEQ ID NO: 1457) having a hairpin-like structure as a precursor is known.
- hsa-miR-4433a-3p gene or “hsa-miR-4433a-3p” refers to the hsa-miR-4433a-3p gene (miRBase Accession No. 1) described in SEQ ID NO: 1439. MIMAT0018949) and other species homologs or orthologs.
- the hsa-miR-4433a-3p gene is described in Jim DD et al., 2010, Blood. 116, e118-e127.
- “hsa-miR-4433a-3p” is known as “hsa-miR-4433a-3p” (miRBase Accession No. MI0016773, SEQ ID NO: 1458) having a hairpin-like structure as a precursor.
- hsa-miR-4485-3p gene or “hsa-miR-4485-3p” refers to the hsa-miR-4485-3p gene described in SEQ ID NO: 1440 (miRBase Accession No. MIMAT0019019) and other species homologues or orthologues are included.
- the hsa-miR-4485-3p gene is described in Jim DD et al., 2010, Blood. 116, e118-e127.
- “hsa-miR-4485-3p” is known as “hsa-miR-4485-3p” (miRBase Accession No. MI0016846, SEQ ID NO: 1459) having a hairpin-like structure as a precursor.
- hsa-miR-6831-5p gene or “hsa-miR-6831-5p” refers to the hsa-miR-6831-5p gene described in SEQ ID NO: 1441 (miRBase Accession No. MIMAT0027562) and other species homologues or orthologues are included.
- the hsa-miR-6831-5p gene is described in Ladewig E et al., 2012, Genome Res. , Vol. 22, 1634-1645.
- “hsa-miR-6831-5p” is known as “hsa-miR-6831-5p” (miRBase Accession No. MI0022676, SEQ ID NO: 1460) having a hairpin-like structure as a precursor.
- hsa-miR-519c-5p gene or “hsa-miR-519c-5p” refers to the hsa-miR-519c-5p gene described in SEQ ID NO: 1442 (miRBase Accession No. MIMAT0002831) and other species homologs or orthologs are included.
- the hsa-miR-519c-5p gene was obtained from Bentwich I et al., 2005, Nat Genet. 37, 766-770.
- “hsa-miR-519c-5p” “hsa-miR-519c-5p” (miRBase Accession No. MI0003148, SEQ ID NO: 1461) having a hairpin-like structure as a precursor is known.
- hsa-miR-551b-5p gene or “hsa-miR-551b-5p” refers to the hsa-miR-551b-5p gene (miRBase Accession No. 1) described in SEQ ID NO: 1443. MIMAT0004794) and other species homologs or orthologs.
- the hsa-miR-551b-5p gene was found in Cummins JM et al., 2006, Proc Natl Acad Sci US A. 103, 3687-3692 can be obtained.
- “hsa-miR-551b-5p” “hsa-miR-551b-5p” (miRBase Accession No. MI0003575, SEQ ID NO: 1462) having a hairpin-like structure as a precursor is known.
- hsa-miR-1343-3p gene or “hsa-miR-1343-3p” refers to the hsa-miR-1343-3p gene (miRBase Accession No. 1) described in SEQ ID NO: 1444. MIMAT0019776) and other species homologs or orthologs.
- the hsa-miR-1343-3p gene is disclosed in Persson H et al., 2011, Cancer Res. , 71, 78-86.
- “Hsa-miR-1343-3p” is known as “hsa-miR-1343-3p” (miRBase Accession No. MI0017320, SEQ ID NO: 1463) having a hairpin-like structure as a precursor.
- hsa-miR-4286 gene or “hsa-miR-4286” refers to the hsa-miR-4286 gene (miRBase Accession No. MIMAT0016916) described in SEQ ID NO: 1445 or other biological species. Homologs or orthologs are included. The hsa-miR-4286 gene was found in Goff LA et al., 2009, PLoS One. 4 can be obtained by the method described in e7192. As for “hsa-miR-4286”, “hsa-miR-4286” (miRBase Accession No. MI0015894, SEQ ID NO: 1464) having a hairpin-like structure as a precursor is known.
- hsa-miR-4634 gene or “hsa-miR-4634” refers to the hsa-miR-4634 gene (miRBase Accession No. MIMAT0019691) described in SEQ ID NO: 1446 or other biological species. Homologs or orthologs are included.
- the hsa-miR-4634 gene is disclosed in Persson H et al., 2011, Cancer Res. , 71, 78-86.
- hsa-miR-4634 “hsa-miR-4634” (miRBase Accession No. MI0017261, SEQ ID NO: 1465) having a hairpin-like structure as a precursor is known.
- hsa-miR-4733-3p gene or “hsa-miR-4733-3p” refers to the hsa-miR-4733-3p gene (miRBase Accession No. 1) described in SEQ ID NO: 1447. MIMAT0019858) and other species homologs or orthologs.
- the hsa-miR-4733-3p gene is disclosed in Persson H et al., 2011, Cancer Res. , 71, 78-86.
- “hsa-miR-4733-3p” is known as “hsa-miR-4733-3p” (miRBase Accession No. MI0017370, SEQ ID NO: 1466) having a hairpin-like structure as a precursor.
- hsa-miR-6086 gene or “hsa-miR-6086” refers to the hsa-miR-6086 gene (miRBase Accession No. MIMAT0023711) described in SEQ ID NO: 1448 and other biological species. Homologs or orthologs are included.
- the hsa-miR-6086 gene was obtained from Yoo JK et al., 2012, Stem Cells Dev. 21 and 2049-2057.
- hsa-miR-6086 is known as “hsa-miR-6086” (miRBase Accession No. MI0020363, SEQ ID NO: 1467) having a hairpin-like structure as a precursor.
- hsa-miR-30d-5p gene or “hsa-miR-30d-5p” refers to the hsa-miR-30d-5p gene described in SEQ ID NO: 1449 (miRBase Accession No. MIMAT000045) and other species homologues or orthologues are included.
- the hsa-miR-30d-5p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. , Vol. 12, 735-739.
- “hsa-miR-30d-5p” is known as “hsa-miR-30d-5p” (miRBase Accession No. MI0000255, SEQ ID NO: 1468) having a hairpin-like structure as a precursor.
- hsa-miR-30b-3p gene or “hsa-miR-30b-3p” refers to the hsa-miR-30b-3p gene (miRBase Accession No. 1) described in SEQ ID NO: 1450. MIMAT0004589) and other species homologues or orthologues are included.
- the hsa-miR-30b-3p gene was obtained from Lagos-Quintana M et al., 2002, Curr Biol. , Vol. 12, 735-739.
- “hsa-miR-30b-3p” is known as “hsa-miR-30b-3p” (miRBase Accession No. MI000000441, SEQ ID NO: 1469) having a hairpin-like structure as a precursor.
- hsa-miR-92a-3p gene or “hsa-miR-92a-3p” refers to the hsa-miR-92a-3p gene (miRBase Accession No. 1) described in SEQ ID NO: 1451. MIMAT00000092) and other species homologs or orthologs.
- the hsa-miR-92a-3p gene is described in Mouretos Z et al., 2002, Genes Dev. 16 can be obtained by the method described in 720-728.
- “hsa-miR-92a-3p” is known as “hsa-miR-92a-3p” (miRBase Accession No. MI00000093, SEQ ID NO: 1470) having a hairpin-like structure as a precursor.
- hsa-miR-371b-5p gene or “hsa-miR-371b-5p” refers to the hsa-miR-371b-5p gene described in SEQ ID NO: 1452 (miRBase Accession No. MIMAT0019892) and other species homologs or orthologs are included.
- the hsa-miR-371b-5p gene is described in Persson H et al., 2011, Cancer Res. , 71, 78-86.
- “hsa-miR-371b-5p” is known as “hsa-miR-371b-5p” (miRBase Accession No. MI0017393, SEQ ID NO: 1471) having a hairpin-like structure as a precursor.
- hsa-miR-486-5p gene or “hsa-miR-486-5p” refers to the hsa-miR-486-5p gene (miRBase Accession No. 1) described in SEQ ID NO: 1453. MIMAT0002177) and other species homologues or orthologues are included.
- the hsa-miR-486-5p gene was obtained from Fu H et al., 2005, FEBS Lett. 579, 3849-3854.
- “hsa-miR-486-5p” “hsa-miR-486-5p” (miRBase Accession No. MI0002470, SEQ ID NO: 1472) having a hairpin-like structure as a precursor is known.
- mature miRNA When mature miRNA is cleaved as a mature miRNA from an RNA precursor having a hairpin-like structure, one to several bases before or after the sequence may be cut out, or may be mutated due to base substitution. It can become a body and is referred to as isomiR (Morin RD. Et al., 2008, Genome Res., Vol. 18, p.610-621).
- miRBBase version 21
- any of a number of SEQ ID NOs: 783-1314 called isomiR variants and fragments of the base sequence represented by These mutants can also be obtained as miRNA having the base sequence represented by any of SEQ ID NOs: 1-210, 211-249, 250-374, and 375-390. That is, SEQ ID NOs: 3, 4, 5, 6, 7, 8, 10, 11, 12, 13, 15, 16, 17, 19, 22, 23, 25, 26, 28, 29, 30, 31 of the present invention.
- polynucleotide examples include sequences represented by 208, 213, 218, 235, 350, and 386.
- the polynucleotides that are numerous isomiRs of SEQ ID NOs: 1-210, 211-249, 250-374, and 375-390 registered in miRBase can be mentioned.
- examples of the polynucleotide containing the base sequence represented by any one of SEQ ID NOs: 1-210, 211-249, 250-374, and 375-390 include any of SEQ ID NOs: 391 to 782, which are precursors, respectively.
- the polynucleotide represented by these is mentioned.
- miRBBase version 21
- miRBBase version 21
- a number of sequence numbers called isomiR Variants and fragments of the nucleotide sequences represented by any of 1015 to 1017, 1019 to 1024, 1026 to 1031, 1285 to 1286, and 1400 to 1434 are also shown.
- miRNAs having the base sequences represented by any of SEQ ID NOs: 194 to 210, 374, and 1315 to 1350, and 211 to 212 and 1351 to 1356.
- the longest mutant registered in 21) includes a polynucleotide represented by SEQ ID NO: 1427.
- the shortest variants are SEQ ID NOs: 1017, 1020, 1405, 1022, 1407, 1409, 1411, 1024, 1027, 1415, 1417, 1418, 1419, 1029, 1421, 1428, 1430, 1432, respectively.
- a polynucleotide having the sequence represented by 1434 there are polynucleotides that are registered in miRBase and are numerous isomiRs of SEQ ID NOs: 194 to 210, 374, and 1315 to 1350, and 211 to 212 and 1351 to 1356. .
- the precursors of SEQ ID NOs: 398 and 490 are used. , 591, 593 to 609, 766, and 1357 to 1399.
- miRBBase version 21
- isomiR Mutants and fragments of are also shown. These mutants can also be obtained as miRNA having the base sequence represented by any of SEQ ID NOs: 1435 to 1448 and 1449 to 1453.
- polynucleotide variants having a base sequence in which u is t in the sequence for example, the longest variant registered in miRBBase (Version 21) includes the polynucleotide represented by SEQ ID NO: 1496.
- examples of the shortest mutant include polynucleotides having sequences represented by SEQ ID NOs: 1494, 1501, and 1505, respectively.
- polynucleotides that are numerous isomiRs of SEQ ID NOs: 1435 to 1448 and 1449 to 1453 registered in miRBase can be mentioned.
- polynucleotide containing the base sequence represented by any one of SEQ ID NOs: 1435 to 1448 and 1449 to 1453 the polynucleotide represented by any one of SEQ ID NOs: 1454 to 1467 and 1468 to 1472 as precursors Nucleotides are mentioned.
- nucleic acid probe or primer used in the present invention binds to a specific target nucleic acid and cannot substantially bind to another nucleic acid.
- the present invention it is possible to detect dementia of a wide range of disease types comprehensively with high accuracy (or AUC), sensitivity, and specificity, and to distinguish between dementia and normal cognitive function (non-dementia). Become.
- AUC accuracy
- sensitivity sensitivity
- specificity sensitivity
- specificity sensitivity
- specificity sensitivity
- specificity sensitivity
- specificity normal cognitive function
- a dementia disease type easily and without differences between doctors and medical institutions. For example, whether or not a subject is easily demented by using as an index a measured value of the expression level of one or more to several miRNAs in the blood, serum and / or plasma of a subject that can be collected minimally invasively Can be detected.
- FIG. 1 shows hsa-miR-4728-5p represented by SEQ ID NO: 3 generated from hsa-mir-4728 represented by SEQ ID NO: 393, and hsa-miR represented by SEQ ID NO: 335. This shows the relationship of the base sequence of ⁇ 4728-3p.
- FIG. 2 is a discrimination score diagram of the learning sample group and the verification sample group obtained in Example 1. 2A shows Alzheimer's dementia obtained in Example 1-1, FIG. 2B shows vascular dementia obtained in Example 1-2, and FIG. 2C shows Lewy body type recognition obtained in Example 1-3. FIG. FIG. FIG. FIG.
- FIG. 3 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 2-1, and ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 4 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 2-2, and the ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 5 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 2-3, and the ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 6 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 2-4, and ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 7 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 2-5, and ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 8 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 3-1, and ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 9 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 3-2, and ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 10 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 3-3, and the ROC curve of the learning sample group (C) and the verification sample group (D).
- FIG. 11 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 3-4, and ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 12 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 3-5, and ROC curves of the learning sample group (C) and the verification sample group (D).
- FIG. 13 is an ROC curve of the verification sample group obtained in Example 9.
- FIG. 13A shows Alzheimer type dementia obtained in Example 9-1
- FIG. 13B shows vascular dementia obtained in Example 9-2
- FIG. 13C shows Lewy body type recognition obtained in Example 9-3.
- FIG. FIG. 14 shows the nucleotide sequence of hsa-miR-6765-5p generated from hsa-mir-6765 represented by SEQ ID NO: 490, and hsa-miR-6765-3p represented by SEQ ID NO: 1315. The relationship is shown.
- FIG. 15 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 15.
- FIG. 16 is a discrimination score diagram of the learning sample group (A) and the verification sample group (B) obtained in Example 20.
- FIG. 17 is a diagram showing the ROC curve obtained in Example 21.
- FIG. 17A is an ROC in which the sensitivity calculated using 42 miRNA markers obtained in Example 15 and 51 miRNA markers obtained in Example 20 are plotted on the vertical axis and the specificity is plotted on the horizontal axis. It is a curve.
- FIG. 18A is a discrimination score diagram of the verification sample group using 44 miRNA markers obtained in Example 24, and
- FIG. 18B is a longitudinal graph showing the sensitivity calculated using 44 miRNA markers obtained in Example 24. It is a ROC curve with the axis representing the specificity and the abscissa representing the specificity.
- Target nucleic acid for dementia Main target nucleic acid as a dementia marker for detecting the presence or absence of dementia or dementia using the nucleic acid probe or primer for detection of dementia as defined above of the present invention (I) miR-4274, miR-4272, miR-4728-5p, miR-4443, miR-4506, miR-6773-5p, miR-4662a-5p, miR-3184-3p, miR-4281, miR-320d, miR-6729-3p, miR-5192, miR-6683-5p, miR-1234-3p, miR-12233-3p, miR-4539, miR-3914, miR-4438-5p, miR-548au- 3p, miR-1539, miR-4720-3p, miR-365b-5p, miR-4 486, miR-1227-5p, miR-4667-5p, miR-6088, miR-6820-5p, miR-4505, miR-548q, miR-4658, miR-
- miRNAs that can be combined with these miRNA (i): (ii) miR-1225-3p, miR-3184-5p, miR-665, miR-211-5p, miR-1247-5p MiR-3656, miR-149-5p, miR-744-5p, miR-345-5p, miR-150-5p, miR-191-3p, miR-651-5p, miR-34a-5p, miR-409 -5p, miR-369-5p, miR-1915-5p, miR-204-5p, miR-137, miR-382-5p, miR-517-5p, miR-532-5p, miR-22-5p, miR -1237-3p, miR-1224-3p, miR-625-3p, miR-328-3p, miR 122-5p, miR-202-3p, miR-4781-5p, miR-718, miR-342-3p, miR-26b-3p, miR-140-3p, miR-200a-3p, miRNA
- miRNA-4728-5p miRNA (i) to (ii) or separately from the miRNA (i) to (ii), (iii) miR-4728-5p, miR-3184-3p, miR-12233-3p, miR- 6088, miR-6777-3p, miR-7110-3p, miR-936, miR-6087, miR-1202, miR-4731-3p, miR-4800-5p, miR-6784-3p, miR-4716-5p, miR-6734-3p, miR-6889-3p, miR-6867-3p, miR-3622a-3p, miR-6813-3p, miR-4769-3p, miR-5698, miR-3184-5p, miR-1471, miR-1538, miR-449b-3p, miR-1976, miR-4268, m R-4279, miR-3620-3p, miR-3944-3p, miR-3156-3p, miR-3187-5p, miR-44
- Other dementia markers that can be combined with the miRNAs (i) to (iii) include: (iv) miR-766-3p, miR-1229-3p, miR-1306-5p, miR-210-5p, miR- 198, miR-485-3p, miR-668-3p, miR-532-3p, miR-877-3p, miR-1238-3p, miR-3130-5p, miR-4298, miR-4290, miR-3343, One, two, three or more, ten or more, preferably three to 110 miRNAs selected from the group consisting of miR-346 and miR-767-3p can also be preferably used as the target nucleic acid.
- the miRNA includes, for example, a nucleotide sequence represented by any one of SEQ ID NOs: 1-210, 211-249, 250-374, 375-390, 1315-1350, 1351-1356, 1435-1448, 1449-1453 (I.e., miR-4274, miR-4272, miR-4728-5p, miR-4443, miR-4506, miR-6773-5p, miR-4662a-5p, miR-3184-3p, miR, respectively) -4281, miR-320d, miR-6729-3p, miR-5192, miR-6683-5p, miR-1234-3p, miR-1233-3p, miR-4539, miR-3914, miR-4438-5p, miR -548au-3p, miR-1539, iR-4720-3p, miR-365b-5p, miR-4486, miR-1227-5p, miR-4667-5p, miR-6088, miR-6820
- Preferred target nucleic acids include the nucleotide sequences represented by any of SEQ ID NOs: 1-210, 211-249, 250-374, and 375-390, 1315-1350, 1351-1356, 1435-1448, 1449-1453. It is a human gene, its transcription product, more preferably the transcription product, ie, miRNA, its precursor RNA, pri-miRNA or pre-miRNA.
- the nucleic acid probe or primer for detecting dementia as defined above of the present invention is used as a major dementia marker for detecting the presence or absence of dementia or dementia.
- the target nucleic acids include miR-5698, miR-1915-3p, miR-1343-5p, miR-6861-5p, miR-6781-5p, miR-4508, miR-6743-5p, miR-6726-5p, miR -4525, miR-4651, miR-6683-5p, miR-5787, miR-1290, miR-6075, miR-4758-5p, miR-4690-5p, miR-762, miR-371a-5p, miR-6765 -3p, miR-6784-5p, miR-6778-5p, miR-6875-5p miR-4534, miR-4721, miR-6756-5p, miR-615-5p, miR-6727-5p, miR-6687-5p, miR-8063, miR-68
- the miRNA includes, for example, human genes containing the nucleotide sequences represented by any of SEQ ID NOs: 194 to 210, 374, and 1315 to 1350, and 211 to 212 and 1351 to 1356 (ie, miR-5698, respectively).
- the target nucleic acid is a human gene comprising a nucleotide sequence represented by any of SEQ ID NOs: 194 to 210, 374, and 1315 to 1350, and 211 to 212 and 1351 to 1356, a transcription product thereof, more preferably Is the transcript, ie miRNA, its precursor RNA, pri-miRNA or pre-miRNA.
- the first target gene is the hsa-miR-4274 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the second target gene is the hsa-miR-4272 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the third target gene is the hsa-miR-4728-5p gene, their homologues, their transcripts, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the fourth target gene is the hsa-miR-4443 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the fifth target gene is the hsa-miR-4506 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the sixth target gene is the hsa-miR-6773-5p gene, their homologues, their transcription products, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the seventh target gene is the hsa-miR-4662a-5p gene, their homologues, their transcription products, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the eighth target gene is the hsa-miR-3184-3p gene, their homologues, their transcripts, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the ninth target gene is the hsa-miR-4281 gene, their homologs, their transcripts, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the tenth target gene is the hsa-miR-320d gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the eleventh target gene is the hsa-miR-6729-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the twelfth target gene is the hsa-miR-5192 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the thirteenth target gene is an hsa-miR-6683-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 14th target gene is an hsa-miR-1234-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the fifteenth target gene is the hsa-miR-1233-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the sixteenth target gene is an hsa-miR-4539 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 17th target gene is the hsa-miR-3914 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 18th target gene is the hsa-miR-4738-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the nineteenth target gene is the hsa-miR-548au-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the twentieth target gene is the hsa-miR-1539 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 21st target gene is the hsa-miR-4720-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 22nd target gene is the hsa-miR-365b-5p gene, their homologues, their transcripts, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 23rd target gene is the hsa-miR-4486 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 24th target gene is the hsa-miR-1227-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 25th target gene is the hsa-miR-4667-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the twenty-sixth target gene is the hsa-miR-6088 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 27th target gene is the hsa-miR-6820-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 28th target gene is the hsa-miR-4505 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 29th target gene is the hsa-miR-548q gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 30th target gene is the hsa-miR-4658 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the thirty-first target gene is the hsa-miR-450a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the thirty-second target gene is the hsa-miR-1260b gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 33rd target gene is the hsa-miR-3777-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 34th target gene is the hsa-miR-6777-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 35th target gene is the hsa-miR-6826-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the thirty-sixth target gene is the hsa-miR-6683-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 37th target gene is the hsa-miR-4725-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 38th target gene is the hsa-miR-7161-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 39th target gene is the hsa-miR-2277-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 40th target gene is the hsa-miR-7110-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 41st target gene is the hsa-miR-4312 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the forty second target gene is the hsa-miR-4461 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 43rd target gene is the hsa-miR-6766-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 44th target gene is the hsa-miR-1266-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 45th target gene is the hsa-miR-6729-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 46th target gene is the hsa-miR-526b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 47th target gene is an hsa-miR-519e-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 48th target gene is the hsa-miR-512-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 49th target gene is an hsa-miR-5088-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 50th target gene is the hsa-miR-1909-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 51st target gene is the hsa-miR-6511a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 52nd target gene is the hsa-miR-4734 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 53rd target gene is the hsa-miR-936 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 54th target gene is the hsa-miR-1249-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 55th target gene is the hsa-miR-6777-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 56th target gene is the hsa-miR-4487 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 57th target gene is the hsa-miR-3155a gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 58th target gene is the hsa-miR-563 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 59th target gene is the hsa-miR-4741 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 60th target gene is the hsa-miR-6788-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 61st target gene is the hsa-miR-4433b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 62nd target gene is the hsa-miR-323a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 63rd target gene is an hsa-miR-6811-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 64th target gene is the hsa-miR-6721-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 65th target gene is the hsa-miR-5004-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 66th target gene is the hsa-miR-6509-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 67th target gene is the hsa-miR-648 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 68th target gene is the hsa-miR-3913 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 69th target gene is the hsa-miR-6087 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 70th target gene is an hsa-miR-1470 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 71st target gene is an hsa-miR-586 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 72nd target gene is the hsa-miR-3150a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 73rd target gene is the hsa-miR-105-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 74th target gene is the hsa-miR-7793 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 75th target gene is the hsa-miR-1914-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 76th target gene is the hsa-miR-4749-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 77th target gene is the hsa-miR-15b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 78th target gene is the hsa-miR-1289 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 79th target gene is the hsa-miR-4433a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 80th target gene is the hsa-miR-3666 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 81st target gene is the hsa-miR-3186-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 82nd target gene is the hsa-miR-4725-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 83rd target gene is the hsa-miR-4488 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 84th target gene is the hsa-miR-4474-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 85th target gene is the hsa-miR-6673-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 86th target gene is the hsa-miR-4640-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 87th target gene is the hsa-miR-202-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 88th target gene is the hsa-miR-6816-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 89th target gene is the hsa-miR-638 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 90th target gene is the hsa-miR-6821-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 91st target gene is the hsa-miR-1247-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 92nd target gene is the hsa-miR-6765-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 93rd target gene is an hsa-miR-6800-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 94th target gene is the hsa-miR-3928-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 95th target gene is the hsa-miR-3940-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 96th target gene is the hsa-miR-3960 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 97th target gene is the hsa-miR-6775-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 98th target gene is the hsa-miR-3178 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 99th target gene is the hsa-miR- 1202 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 100th target gene is the hsa-miR-6790-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 101st target gene is the hsa-miR-4731-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 102nd target gene is the hsa-miR-2681-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 103rd target gene is the hsa-miR-6758-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 104th target gene is the hsa-miR-8072 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 105th target gene is the hsa-miR-518d-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 106th target gene is the hsa-miR-3606-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 107th target gene is the hsa-miR-4800-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 108th target gene is the hsa-miR-1292-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 109th target gene is the hsa-miR-6784-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 110th target gene is the hsa-miR-4450 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 111th target gene is the hsa-miR-6132 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 112th target gene is the hsa-miR-4716-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 113th target gene is the hsa-miR-6860 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 114th target gene is the hsa-miR-1268b gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 115th target gene is the hsa-miR-378d gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 116th target gene is the hsa-miR-4701-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 117th target gene is the hsa-miR-4329 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 118th target gene is the hsa-miR-185-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 119th target gene is the hsa-miR-552-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 120th target gene is the hsa-miR-1273g-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 121st target gene is the hsa-miR-6769b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 122nd target gene is the hsa-miR-520a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 123rd target gene is the hsa-miR-4524b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 124th target gene is the hsa-miR-4291 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 125th target gene is the hsa-miR-6734-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 126th target gene is the hsa-miR-143-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 127th target gene is the hsa-miR-939-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 128th target gene is the hsa-miR-6889-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 129th target gene is the hsa-miR-6842-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 130th target gene is the hsa-miR-4511 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 131st target gene is the hsa-miR-4318 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 132nd target gene is the hsa-miR-4653-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 133rd target gene is the hsa-miR-6867-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 134th target gene is the hsa-miR-133b gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 135th target gene is the hsa-miR-3196 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 136th target gene is the hsa-miR-193b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 137th target gene is the hsa-miR-3162-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 138th target gene is the hsa-miR-6819-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 139th target gene is the hsa-miR-1908-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 140th target gene is the hsa-miR-6786-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 141st target gene is the hsa-miR-3648 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 142nd target gene is the hsa-miR-4513 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 143 is the hsa-miR-3652 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 144th target gene is the hsa-miR-4640-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 145th target gene is the hsa-miR-6871-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 146th target gene is the hsa-miR-7845-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 147th target gene is the hsa-miR-3138 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 148th target gene is the hsa-miR-6884-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 149th target gene is the hsa-miR-4653-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 150th target gene is the hsa-miR-636 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 151st target gene is the hsa-miR-4652-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 152th target gene is the hsa-miR-6823-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 153rd target gene is the hsa-miR-4502 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 154th target gene is the hsa-miR-7113-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 155th target gene is the hsa-miR-8087 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 156th target gene is the hsa-miR-7154-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 157th target gene is the hsa-miR-5189-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 158th target gene is the hsa-miR-1253 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 159th target gene is the hsa-miR-518c-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 160th target gene is the hsa-miR-7151-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 161st target gene is the hsa-miR-3614-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 162nd target gene is the hsa-miR-4727-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 163rd target gene is the hsa-miR-3682-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 164th target gene is an hsa-miR-5090 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 165th target gene is the hsa-miR-337-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 166th target gene is the hsa-miR-488-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 167th target gene is an hsa-miR-100-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 168th target gene is the hsa-miR-4520-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 169th target gene is the hsa-miR-373-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 170th target gene is the hsa-miR-6499-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 171st target gene is the hsa-miR-3909 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 172nd target gene is the hsa-miR-32-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 173rd target gene is the hsa-miR-302a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 174th target gene is the hsa-miR-4686 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 175th target gene is the hsa-miR-4659a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 176th target gene is the hsa-miR-4287 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 177th target gene is an hsa-miR-1301-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 178th target gene is the hsa-miR-593-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 179th target gene is the hsa-miR-517a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 180th target gene is the hsa-miR-517b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 181 is the hsa-miR-142-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 182nd target gene is the hsa-miR-1185-2-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 183rd target gene is an hsa-miR-602 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 184th target gene is the hsa-miR-527 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 185th target gene is the hsa-miR-518a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 186th target gene is the hsa-miR-4682 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 187th target gene is an hsa-miR-28-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 188th target gene is the hsa-miR-4252 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 189th target gene is the hsa-miR-452-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 190th target gene is the hsa-miR-525-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 191st target gene is the hsa-miR-3622a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 192nd target gene is the hsa-miR-6813-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 193rd target gene is the hsa-miR-4769-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 194th target gene is the hsa-miR-5698 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 195th target gene is the hsa-miR-1915-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 196th target gene is the hsa-miR-1343-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 197th target gene is the hsa-miR-6861-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 198th target gene is the hsa-miR-6781-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 199th target gene is the hsa-miR-4508 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 200th target gene is the hsa-miR-6743-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 201st target gene is the hsa-miR-6726-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 202nd target gene is the hsa-miR-4525 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 203rd target gene is the hsa-miR-4651 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 204th target gene is the hsa-miR-6813-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 205th target gene is the hsa-miR-5787 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 206th target gene is an hsa-miR-1290 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 207th target gene is the hsa-miR-6075 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 208th target gene is the hsa-miR-4758-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 209th target gene is the hsa-miR-4690-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 210th target gene is the hsa-miR-762 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 211st target gene is the hsa-miR-1225-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 212th target gene is the hsa-miR-3184-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 213rd target gene is the hsa-miR-665 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 3).
- the 214th target gene is the hsa-miR-211-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- the 215th target gene is the hsa-miR-1247-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 216th target gene is the hsa-miR-3656 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 217th target gene is the hsa-miR-149-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 218th target gene is the hsa-miR-744-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 6).
- the 219th target gene is the hsa-miR-345-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 3).
- the 220th target gene is an hsa-miR-150-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the target gene 221 is the hsa-miR-191-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 2.
- the 222nd target gene is the hsa-miR-651-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- the 223rd target gene is the hsa-miR-34a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- the 224th target gene is an hsa-miR-409-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 225th target gene is the hsa-miR-369-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 226th target gene is the hsa-miR-1915-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 227th target gene is the hsa-miR-204-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 228th target gene is the hsa-miR-137 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 4).
- the 229th target gene is the hsa-miR-382-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 3).
- the 230th target gene is an hsa-miR-517-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- the target gene 231 is the hsa-miR-532-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a homologue thereof a transcription product thereof, or a mutant or derivative thereof.
- changes in the expression of genes or their transcripts can serve as markers for dementia (US Patent Application Publication No. 2016/0273040).
- the 232th target gene is the hsa-miR-22-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- changes in the expression of a gene or its transcription product can serve as a marker for dementia (International Patent No. 2017/186719).
- the 233rd target gene is the hsa-miR-1237-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 234th target gene is the hsa-miR-1224-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 235th target gene is the hsa-miR-625-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 1.
- the 236th target gene is the hsa-miR-328-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 237th target gene is the hsa-miR-122-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 238th target gene is the hsa-miR-202-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 239th target gene is the hsa-miR-4781-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- the 240th target gene is an hsa-miR-718 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the target gene 241 is the hsa-miR-342-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. There has been a report that changes in the expression of a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 3).
- the 242nd target gene is an hsa-miR-26b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- genes or their transcripts can be markers for dementia (Satoh J., et al., Biomark Insights., 2015, vol. 10, p. 21-). 23).
- the 243rd target gene is the hsa-miR-140-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 1.
- the 244th target gene is the hsa-miR-200a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- changes in the expression of a gene or its transcription product can serve as a marker for dementia (International Patent No. 2017/186719).
- the 245th target gene is the hsa-miR-378a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 246th target gene is the hsa-miR-484 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 1.
- the target gene 247 is the hsa-miR-296-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. There has been a report that changes in the expression of a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 248th target gene is the hsa-miR-205-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 249th target gene is the hsa-miR-431-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 250th target gene is the hsa-miR-1471 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 251st target gene is the hsa-miR-1538 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 252nd target gene is the hsa-miR-449b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 253rd target gene is the hsa-miR-1976 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 254th target gene is the hsa-miR-4268 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 255th target gene is the hsa-miR-4279 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 256th target gene is the hsa-miR-3620-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 257th target gene is the hsa-miR-3944-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 258th target gene is the hsa-miR-3156-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 259th target gene is the hsa-miR-3187-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 260th target gene is the hsa-miR-4485-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 261 is the hsa-miR-4695-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 262th target gene is the hsa-miR-4697-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 263rd target gene is the hsa-miR-4713-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 264th target gene is the hsa-miR-4723-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 265th target gene is the hsa-miR-371b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 266th target gene is the hsa-miR-3151-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 267 is the hsa-miR-3192-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 268th target gene is the hsa-miR-6728-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 269th target gene is the hsa-miR-6736-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 270th target gene is the hsa-miR-6740-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 271st target gene is the hsa-miR-6741-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 272nd target gene is the hsa-miR-6743-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 273rd target gene is the hsa-miR-6747-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 274th target gene is the hsa-miR-6750-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 275th target gene is the hsa-miR-6754-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 276th target gene is the hsa-miR-6759-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 277th target gene is the hsa-miR-6761-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 278th target gene is the hsa-miR-6762-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 279th target gene is the hsa-miR-6769a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 280th target gene is the hsa-miR-6767-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 281st target gene is the hsa-miR-6778-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 282nd target gene is the hsa-miR-6679-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 283rd target gene is the hsa-miR-6786-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 284th target gene is the hsa-miR-6787-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 285th target gene is the hsa-miR-6792-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 286th target gene is the hsa-miR-6794-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 287th target gene is the hsa-miR-6801-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 288th target gene is the hsa-miR-6802-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 289th target gene is the hsa-miR-6803-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 290th target gene is the hsa-miR-6804-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 291st target gene is the hsa-miR-6810-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 292th target gene is the hsa-miR-6823-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 293rd target gene is the hsa-miR-6825-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 294th target gene is the hsa-miR-6829-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 295th target gene is the hsa-miR-6833-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 296th target gene is the hsa-miR-6834-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 297th target gene is the hsa-miR-6780b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 298th target gene is the hsa-miR-6845-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 299th target gene is the hsa-miR-6862-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 300th target gene is the hsa-miR-6865-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 301st target gene is the hsa-miR-6870-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 302nd target gene is the hsa-miR-6875-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 303rd target gene is the hsa-miR-6877-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 304th target gene is the hsa-miR-6879-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 305th target gene is the hsa-miR-6882-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 306th target gene is the hsa-miR-6885-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 307th target gene is the hsa-miR-6886-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 308th target gene is the hsa-miR-6687-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 309th target gene is the hsa-miR-6890-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 310th target gene is the hsa-miR-6893-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 311st target gene is the hsa-miR-6894-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 312rd target gene is the hsa-miR-7106-3p gene, their homologs, their transcripts, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 313 is the hsa-miR-7109-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 314th target gene is the hsa-miR-7114-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 315th target gene is the hsa-miR-7155-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 316th target gene is an hsa-miR-7160-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 317th target gene is the hsa-miR-615-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 318th target gene is the hsa-miR-920 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 319th target gene is the hsa-miR-1825 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 320th target gene is the hsa-miR-675-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- 321st target gene is hsa-miR-1910-5p gene, homologues thereof, transcripts thereof, or mutants or derivatives thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 322th target gene is the hsa-miR-2278 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 323rd target gene is the hsa-miR-2682-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 324th target gene is the hsa-miR-3122 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 325th target gene is the hsa-miR-3151-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 326th target gene is the hsa-miR-3175 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 327th target gene is the hsa-miR-4323 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 328th target gene is the hsa-miR-4326 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 329th target gene is the hsa-miR-4284 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 330th target gene is the hsa-miR-3605-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 331 is the hsa-miR-3622b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 332 is the hsa-miR-3646 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 333rd target gene is the hsa-miR-3158-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 334th target gene is the hsa-miR-4722-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 335th target gene is the hsa-miR-4728-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 336th target gene is the hsa-miR-4747-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 337th target gene is the hsa-miR-4436b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 338th target gene is the hsa-miR-5196-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 339th target gene is the hsa-miR-5589-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 340th target gene is the hsa-miR-345-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 341th target gene is the hsa-miR-642b-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 342 is the hsa-miR-6716-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 343rd target gene is the hsa-miR-6511b-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 344th target gene is the hsa-miR-208a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 345th target gene is the hsa-miR-6726-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 346th target gene is the hsa-miR-6744-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 347th target gene is the hsa-miR-6787-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 348th target gene is the hsa-miR-6789-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 349th target gene is the hsa-miR-6797-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 350th target gene is the hsa-miR-6800-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 351 is the hsa-miR-6806-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 352rd target gene is the hsa-miR-6824-3p gene, their homologues, their transcripts, or their mutants or derivatives. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 353rd target gene is the hsa-miR-6837-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 354th target gene is the hsa-miR-6846-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 355th target gene is the hsa-miR-6858-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 356th target gene is the hsa-miR-6859-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 357th target gene is the hsa-miR-6861-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 358th target gene is the hsa-miR-6880-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 359th target gene is the hsa-miR-7111-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 360th target gene is the hsa-miR-7152-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 361 is the hsa-miR-642a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene of 362 is the hsa-miR-657 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the target gene 363 is the hsa-miR-1236-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 364th target gene is the hsa-miR-764 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 365th target gene is the hsa-miR-4314 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 366th target gene is the hsa-miR-3675-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 367th target gene is the hsa-miR-5703 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 368th target gene is the hsa-miR-3191-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 369th target gene is the hsa-miR-6511a-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 370th target gene is the hsa-miR-6809-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 371st target gene is the hsa-miR-6815-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 372rd target gene is the hsa-miR-6857-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 373rd target gene is the hsa-miR-6878-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 374th target gene is the hsa-miR-371a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 375th target gene is the hsa-miR-766-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 376th target gene is the hsa-miR-1229-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 377th target gene is the hsa-miR-1306-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 6).
- the 378th target gene is the hsa-miR-210-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 379th target gene is the hsa-miR-198 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 380th target gene is the hsa-miR-485-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 7).
- the 381 target gene is the hsa-miR-668-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 4).
- the 382rd target gene is the hsa-miR-532-3p gene, their homologues, their transcription products, or their mutants or derivatives. There has been a report that changes in the expression of a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 383rd target gene is the hsa-miR-877-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 384th target gene is the hsa-miR-1238-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a report that changes in the expression of a gene or a transcription product thereof can be a marker for dementia Patent Document 2.
- the 385th target gene is the hsa-miR-3130-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 386th target gene is the hsa-miR-4298 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 387th target gene is an hsa-miR-4290 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 388th target gene is the hsa-miR-3943 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 389th target gene is the hsa-miR-346 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 3).
- the 390th target gene is the hsa-miR-767-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof.
- a gene or a transcription product thereof can serve as a marker for dementia (Patent Document 5).
- the 391st target gene is the hsa-miR-6765-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 392rd target gene is the hsa-miR-6784-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 393rd target gene is the hsa-miR-6778-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 394th target gene is the hsa-miR-6875-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 395th target gene is the hsa-miR-4534 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 396th target gene is the hsa-miR-4721 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 397th target gene is the hsa-miR-6756-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 398th target gene is the hsa-miR-615-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 399th target gene is the hsa-miR-6727-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 400th target gene is the hsa-miR-6687-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 401st target gene is the hsa-miR-8063 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 402nd target gene is the hsa-miR-6880-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 403rd target gene is the hsa-miR-6805-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 404th target gene is the hsa-miR-4726-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 405th target gene is the hsa-miR-4710 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 406th target gene is the hsa-miR-7111-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 407th target gene is the hsa-miR-3619-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 408th target gene is the hsa-miR-6695-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 409th target gene is the hsa-miR-1254 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 410th target gene is the hsa-miR-1233-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 411st target gene is the hsa-miR-6836-3p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 412 target gene is the hsa-miR-6769a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 413th target gene is the hsa-miR-4532 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 414th target gene is an hsa-miR-365a-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 415th target gene is the hsa-miR-1231 gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
- the 416th target gene is the hsa-miR-1228-5p gene, a homologue thereof, a transcription product thereof, or a mutant or derivative thereof. So far, there is no report that changes in the expression of genes or their transcripts can serve as markers for dementia.
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Abstract
Description
すなわち、本発明は、以下の態様を含む。
(1)認知症マーカーである、miR-4274、miR-4272、miR-4728-5p、miR-4443、miR-4506、miR-6773-5p、miR-4662a-5p、miR-3184-3p、miR-4281、miR-320d、miR-6729-3p、miR-5192、miR-6853-5p、miR-1234-3p、miR-1233-3p、miR-4539、miR-3914、miR-4738-5p、miR-548au-3p、miR-1539、miR-4720-3p、miR-365b-5p、miR-4486、miR-1227-5p、miR-4667-5p、miR-6088、miR-6820-5p、miR-4505、miR-548q、miR-4658、miR-450a-5p、miR-1260b、miR-3677-5p、miR-6777-3p、miR-6826-3p、miR-6832-3p、miR-4725-3p、miR-7161-3p、miR-2277-5p、miR-7110-3p、miR-4312、miR-4461、miR-6766-5p、miR-1266-3p、miR-6729-5p、miR-526b-3p、miR-519e-5p、miR-512-5p、miR-5088-5p、miR-1909-3p、miR-6511a-5p、miR-4734、miR-936、miR-1249-3p、miR-6777-5p、miR-4487、miR-3155a、miR-563、miR-4741、miR-6788-5p、miR-4433b-5p、miR-323a-5p、miR-6811-5p、miR-6721-5p、miR-5004-5p、miR-6509-3p、miR-648、miR-3917、miR-6087、miR-1470、miR-586、miR-3150a-5p、miR-105-3p、miR-7973、miR-1914-5p、miR-4749-3p、miR-15b-5p、miR-1289、miR-4433a-5p、miR-3666、miR-3186-3p、miR-4725-5p、miR-4488、miR-4474-3p、miR-6731-3p、miR-4640-3p、miR-202-5p、miR-6816-5p、miR-638、miR-6821-5p、miR-1247-3p、miR-6765-5p、miR-6800-5p、miR-3928-3p、miR-3940-5p、miR-3960、miR-6775-5p、miR-3178、miR-1202、miR-6790-5p、miR-4731-3p、miR-2681-3p、miR-6758-5p、miR-8072、miR-518d-3p、miR-3606-3p、miR-4800-5p、miR-1292-3p、miR-6784-3p、miR-4450、miR-6132、miR-4716-5p、miR-6860、miR-1268b、miR-378d、miR-4701-5p、miR-4329、miR-185-3p、miR-552-3p、miR-1273g-5p、miR-6769b-3p、miR-520a-3p、miR-4524b-5p、miR-4291、miR-6734-3p、miR-143-5p、miR-939-3p、miR-6889-3p、miR-6842-3p、miR-4511、miR-4318、miR-4653-5p、miR-6867-3p、miR-133b、miR-3196、miR-193b-3p、miR-3162-3p、miR-6819-3p、miR-1908-3p、miR-6786-5p、miR-3648、miR-4513、miR-3652、miR-4640-5p、miR-6871-5p、miR-7845-5p、miR-3138、miR-6884-5p、miR-4653-3p、miR-636、miR-4652-3p、miR-6823-5p、miR-4502、miR-7113-5p、miR-8087、miR-7154-3p、miR-5189-5p、miR-1253、miR-518c-5p、miR-7151-5p、miR-3614-3p、miR-4727-5p、miR-3682-5p、miR-5090、miR-337-3p、miR-488-5p、miR-100-5p、miR-4520-3p、miR-373-3p、miR-6499-5p、miR-3909、miR-32-5p、miR-302a-3p、miR-4686、miR-4659a-3p、miR-4287、miR-1301-5p、miR-593-3p、miR-517a-3p、miR-517b-3p、miR-142-3p、miR-1185-2-3p、miR-602、miR-527、miR-518a-5p、miR-4682、miR-28-5p、miR-4252、miR-452-5p、miR-525-5p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、miR-7114-5p、miR-516a-5p、miR-769-3p、miR-3692-5p、miR-3945、miR-4433a-3p、miR-4485-3p、miR-6831-5p、miR-519c-5p、miR-551b-5p、miR-1343-3p、miR-4286、miR-4634、miR-4733-3p、及びmiR-6086からなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を含む、認知症の検出用キット。
(2)前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(1)に記載のキット。
(3)前記キットが、別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、miR-3665、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p、及びmiR-486-5pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、(1)又は(2)に記載のキット。
(4)前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、(g)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(3)に記載のキット。
(6)前記核酸が、下記の(k)~(o)のいずれかに示すポリヌクレオチド:
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(5)に記載のキット。
(7)前記キットが、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、(1)~(6)のいずれかに記載のキット。
(8)前記核酸が、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(7)に記載のキット。
任意に、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸IIをさらに含む、認知症の検出又は予測用キット。
(10)前記核酸Iが、下記の(u)~(y)のいずれかに示すポリヌクレオチド:
(u)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(v)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列を含むポリヌクレオチド、(w)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(x)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(y)前記(u)~(x)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドであり、
前記核酸IIが、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(9)に記載のキット。
(12)前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(11)に記載のデバイス。
(13)前記デバイスが、別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、miR-3665、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p、及びmiR-486-5pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、(11)又は(12)に記載のデバイス。
(14)前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、(g)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(13)に記載のデバイス。
(16)前記核酸が、下記の(k)~(o)のいずれかに示すポリヌクレオチド:
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(15)に記載のデバイス。
(17)前記デバイスが、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、(11)~(16)のいずれかに記載のデバイス。
(18)前記核酸が、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(17)に記載のデバイス。
任意に、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸IIをさらに含む、認知症の検出又は予測用デバイス。
(20)前記核酸Iが、下記の(u)~(y)のいずれかに示すポリヌクレオチド:
(u)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(v)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列を含むポリヌクレオチド、(w)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(x)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(y)前記(u)~(x)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドであり、
前記核酸IIが、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(19)に記載のデバイス。
(21)前記デバイスが、ハイブリダイゼーション技術による測定のためのデバイスである、(11)~(20)のいずれかに記載のデバイス。
(22)前記ハイブリダイゼーション技術が、核酸アレイ技術である、(21)に記載のデバイス。
(24)認知症であることが既知である被験体由来の検体の遺伝子発現量と非認知症被験体由来の検体の遺伝子発現量を教師サンプルとして作成された、かつ認知症又は非認知症を区別的に判別することが可能である判別式に、上記被験体由来の検体中の前記1以上のポリヌクレオチドの発現量を代入し、それによって、認知症又は非認知症を評価することを含む、(23)に記載の方法。
(25)前記ポリヌクレオチド又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドの発現量の測定を行い、前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(23)又は(24)に記載の方法。
(27)前記ポリヌクレオチド又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドの発現量の測定を行い、前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(26)に記載の方法。
(28)別の認知症マーカーである、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、及びmiR-6878-3pからなる群から選択される1以上のポリヌクレオチドの発現量を測定することをさらに含む、(23)~(27)のいずれかに記載の方法。
(29)前記ポリヌクレオチド又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドの発現量の測定を行い、前記核酸が、下記の(k)~(o)のいずれかに示すポリヌクレオチド:
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(28)に記載のデバイス。
(30)別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、miR-767-3pからなる群から選択される1以上のポリヌクレオチドの発現量を測定することをさらに含む、(23)~(29)のいずれかに記載の方法。
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(30)に記載の方法。
(32)認知症マーカーである、miR-4728-5p、miR-3184-3p、miR-1233-3p、miR-6088、miR-6777-3p、miR-7110-3p、miR-936、miR-6087、miR-1202、miR-4731-3p、miR-4800-5p、miR-6784-3p、miR-4716-5p、miR-6734-3p、miR-6889-3p、miR-6867-3p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-3184-5p、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、miR-6878-3p、及びmiR-371a-5pからなる群から選択される1以上のポリヌクレオチドIの発現量を測定することを含み、
任意に、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチドIIの発現量を測定することをさらに含み、
該測定された発現量を用いて、被験体が認知症に罹患しているか否かをin vitroで評価するか、又は被験体が認知症に罹患する可能性又はin vitroで予測することを含む、認知症の検出又は予測方法。
(33)前記ポリヌクレオチドI又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドIの発現量の測定を行い、前記核酸が、下記の(u)~(y)のいずれかに示すポリヌクレオチド:
(u)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(v)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列を含むポリヌクレオチド、(w)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(x)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(y)前記(u)~(x)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドであり、
前記ポリヌクレオチドII又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドIIの発現量の測定を行い、前記核酸が、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(32)に記載の方法。
(34)(1)~(10)のいずれかに記載のキット又は(11)~(22)のいずれかに記載のデバイスを用いて、被験体の検体における標的遺伝子の発現量を測定する、(23)~(33)のいずれかに記載の方法。
(35)前記被験体が、ヒトである、(23)~(34)のいずれかに記載の方法。
(1’)認知症マーカーである、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、及びmiR-7114-5pからなる群から選択される1以上のポリヌクレオチドと特異的に結合可能な核酸を含む、認知症の検出用キット。
(2’)前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(1’)に記載のキット。
(3’)前記キットが、別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、及びmiR-3665からなる群から選択される1以上のポリヌクレオチドと特異的に結合可能な核酸をさらに含む、(1’)又は(2’)に記載のキット。
(4’)前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~212、及び1351~1356のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(3’)に記載のキット。
(5’)認知症マーカーである、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、及びmiR-7114-5pからなる群から選択される1以上のポリヌクレオチドと特異的に結合可能な核酸を含む、認知症の検出用デバイス。
(6’)前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(5’)に記載のデバイス。
(7’)前記デバイスが、別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、及びmiR-3665からなる群から選択される1以上のポリヌクレオチドと特異的に結合可能な核酸をさらに含む、(5’)又は(6’)に記載のデバイス。
(8’)前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~212、及び1351~1356のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(7’)に記載のデバイス。
(9’)前記デバイスが、ハイブリダイゼーション技術による測定のためのデバイスである、(5’)~(8’)のいずれかに記載のデバイス。
(10’)前記ハイブリダイゼーション技術が、核酸アレイ技術である、(9’)に記載のデバイス。
(11’)認知症マーカーである、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、及びmiR-7114-5pからなる群から選択される1以上のポリヌクレオチドのそれぞれと特異的に結合可能な核酸を含む、(1’)~(4’)のいずれかに記載のキット又は(5’)~(10’)のいずれかに記載のデバイスを用いて、被験体の検体における標的核酸の発現量を測定し、該測定された発現量と、同様に測定された非認知症検体の対照発現量とを用いて、被験体が認知症に罹患しているか否かをin vitroで評価することを含む、認知症の検出方法。
(12’)認知症マーカーである、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、及びmiR-7114-5pからなる群から選択される1以上のポリヌクレオチドのそれぞれと特異的に結合可能な核酸を含む、(1’)~(4’)のいずれかに記載のキット又は(5’)~(10’)のいずれかに記載のデバイスを用いて被験体の検体における標的遺伝子の発現量を測定し、認知症であることが既知である被験体由来の検体の遺伝子発現量と非認知症被験体由来の検体の遺伝子発現量を教師サンプルとして作成された、かつ認知症又は非認知症を区別的に判別することが可能である判別式に、上記被験体由来の検体中の標的遺伝子の発現量を代入し、それによって、認知症又は非認知症を評価することを含む、被験体における認知症を検出する方法。
(13’)前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(11’)又は(12’)に記載の方法。
(14’)前記キット又はデバイスが、別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、及びmiR-3665からなる群から選択される少なくとも1つのポリヌクレオチドと特異的に結合可能な核酸をさらに含む、(11’)~(13’)のいずれかに記載の方法。
(15’)前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~212、及び1351~1356のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~212、及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、(14’)に記載の方法。
(16’)前記被験体が、ヒトである、(11’)~(15’)のいずれかに記載の方法。
(17’)前記検体が、血液、血清又は血漿である、(11’)~(16’)のいずれかに記載の方法。
R-4287であり、miR-1301-5pがhsa-miR-1301-5pであり、miR-593-3pがhsa-miR-593-3pであり、miR-517a-3pがhsa-miR-517a-3pであり、miR-517b-3pがhsa-miR-517b-3pであり、miR-142-3pがhsa-miR-142-3pであり、miR-1185-2-3pがhsa-miR-1185-2-3pであり、miR-602がhsa-miR-602であり、miR-527がhsa-miR-527であり、miR-518a-5pがhsa-miR-518a-5pであり、miR-4682がhsa-miR-4682であり、miR-28-5pがhsa-miR-28-5pであり、miR-4252がhsa-miR-4252であり、miR-452-5pがhsa-miR-452-5pであり、miR-525-5pがhsa-miR-525-5pであり、miR-3622a-3pがhsa-miR-3622a-3pであり、miR-6813-3pがhsa-miR-6813-3pであり、miR-4769-3pがhsa-miR-4769-3pであり、miR-5698がhsa-miR-5698であり、miR-1915-3pがhsa-miR-1915-3pであり、miR-1343-5pがhsa-miR-1343-5pであり、miR-6861-5pがhsa-miR-6861-5pであり、miR-6781-5pがhsa-miR-6781-5pであり、miR-4508がhsa-miR-4508であり、miR-6743-5pがhsa-miR-6743-5pであり、miR-6726-5pがhsa-miR-6726-5pであり、miR-4525がhsa-miR-4525であり、miR-4651がhsa-miR-4651であり、miR-6813-5pがhsa-miR-6813-5pであり、miR-5787がhsa-miR-5787であり、miR-1290がhsa-miR-1290であり、miR-6075がhsa-miR-6075であり、miR-4758-5pがhsa-miR-4758-5pであり、miR-4690-5pがhsa-miR-4690-5pであり、miR-762がhsa-miR-762であり、miR-1225-3pがhsa-miR-1225-3pであり、miR-3184-5pがhsa-miR-3184-5pであり、miR-665がhsa-miR-665であり、miR-211-5pがhsa-miR-211-5pであり、miR-1247-5pがhsa-miR-1247-5pであり、miR-3656がhsa-miR-3656であり、miR-149-5pがhsa-miR-149-5pであり、miR-744-5pがhsa-miR-744-5pであり、miR-345-5pがhsa-miR-345-5pであり、miR-150-5pがhsa-miR-150-5pであり、miR-191-3pがhsa-miR-191-3pであり、miR-651-5pがhsa-miR-651-5pであり、miR-34a-5pがhsa-miR-34a-5pであり、miR-409-5pがhsa-miR-409-5pであり、miR-369-5pがhsa-miR-369-5pであり、miR-1915-5pがhsa-miR-1915-5pであり、miR-204-5pがhsa-miR-204-5pであり、miR-137がhsa-miR-137であり、miR-382-5pがhsa-miR-382-5pであり、miR-517-5pがhsa-miR-517-5pであり、miR-532-5pがhsa-miR-532-5pであり、miR-22-5pがhsa-miR-22-5pであり、miR-1237-3pがhsa-miR-1237-3pであり、miR-1224-3pがhsa-miR-1224-3pであり、miR-625-3pがhsa-miR-625-3pであり、miR-328-3pがhsa-miR-328-3pであり、miR-122-5pがhsa-miR-122-5pであり、miR-202-3pがhsa-miR-202-3pであり、miR-4781-5pがhsa-miR-4781-5pであり、miR-718がhsa-miR-718であり、miR-342-3pがhsa-miR-342-3pであり、miR-26b-3pがhsa-miR-26b-3pであり、miR-140-3pがhsa-miR-140-3pであり、miR-200a-3pがhsa-miR-200a-3pであり、miR-378a-3pがhsa-miR-378a-3pであり、miR-484がhsa-miR-484であり、miR-296-5pがhsa-miR-296-5pであり、miR-205-5pがhsa-miR-205-5pであり、miR-431-5pがhsa-miR-431-5pであり、miR-1471がhsa-miR-1471であり、miR-1538がhsa-miR-1538であり、miR-449b-3pがhsa-miR-449b-3pであり、miR-1976がhsa-miR-1976であり、miR-4268がhsa-miR-4268であり、miR-4279がhsa-miR-4279であり、miR-3620-3pがhsa-miR-3620-3pであり、miR-3944-3pがhsa-miR-3944-3pであり、miR-3156-3pがhsa-miR-3156-3pであり、miR-3187-5pがhsa-miR-3187-5pであり、miR-4685-3pがhsa-miR-4685-3pであり、miR-4695-3pがhsa-miR-4695-3pであり、miR-4697-3pがhsa-miR-4697-3pであり、miR-4713-5pがhsa-miR-4713-5pであり、miR-4723-3pがhsa-miR-4723-3pであり、miR-371b-3pがhsa-miR-371b-3pであり、miR-3151-3pがhsa-miR-3151-3pであり、miR-3192-3pがhsa-miR-3192-3pであり、miR-6728-3pがhsa-miR-6728-3pであり、miR-6736-3pがhsa-miR-6736-3pであり、miR-6740-3pがhsa-miR-6740-3pであり、miR-6741-3pがhsa-miR-6741-3pであり、miR-6743-3pがhsa-miR-6743-3pであり、miR-6747-3pがhsa-miR-6747-3pであり、miR-6750-3pがhsa-miR-6750-3pであり、miR-6754-3pがhsa-miR-6754-3pであり、miR-6759-3pがhsa-miR-6759-3pであり、miR-6761-3pがhsa-miR-6761-3pであり、miR-6762-3pがhsa-miR-6762-3pであり、miR-6769a-3pがhsa-miR-6769a-3pであり、miR-6776-3pがhsa-miR-6776-3pであり、miR-6778-3pがhsa-miR-6778-3pであり、miR-6779-3pがhsa-miR-6779-3pであり、miR-6786-3pがhsa-miR-6786-3pであり、miR-6787-3pがhsa-miR-6787-3pであり、miR-6792-3pがhsa-miR-6792-3pであり、miR-6794-3pがhsa-miR-6794-3pであり、miR-6801-3pがhsa-miR-6801-3pであり、miR-6802-3pがhsa-miR-6802-3pであり、miR-6803-3pがhsa-miR-6803-3pであり、miR-6804-3pがhsa-miR-6804-3pであり、miR-6810-5pがhsa-miR-6810-5pであり、miR-6823-3pがhsa-miR-6823-3pであり、miR-6825-3pがhsa-miR-6825-3pであり、miR-6829-3pがhsa-miR-6829-3pであり、miR-6833-3pがhsa-miR-6833-3pであり、miR-6834-3pがhsa-miR-6834-3pであり、miR-6780b-3pがhsa-miR-6780b-3pであり、miR-6845-3pがhsa-miR-6845-3pであり、miR-6862-3pがhsa-miR-6862-3pであり、miR-6865-3pがhsa-miR-6865-3pであり、miR-6870-3pがhsa-miR-6870-3pであり、miR-6875-3pがhsa-miR-6875-3pであり、miR-6877-3pがhsa-miR-6877-3pであり、miR-6879-3pがhsa-miR-6879-3pであり、miR-6882-3pがhsa-miR-6882-3pであり、miR-6885-3pがhsa-miR-6885-3pであり、miR-6886-3pがhsa-miR-6886-3pであり、miR-6887-3pがhsa-miR-6887-3pであり、miR-6890-3pがhsa-miR-6890-3pであり、miR-6893-3pがhsa-miR-6893-3pであり、miR-6894-3pがhsa-miR-6894-3pであり、miR-7106-3pがhsa-miR-7106-3pであり、miR-7109-3pがhsa-miR-7109-3pであり、miR-7114-3pがhsa-miR-7114-3pであり、miR-7155-5pがhsa-miR-7155-5pであり、miR-7160-5pがhsa-miR-7160-5pであり、miR-615-3pがhsa-miR-615-3pであり、miR-920がhsa-miR-920であり、miR-1825がhsa-miR-1825であり、miR-675-3pがhsa-miR-675-3pであり、miR-1910-5pがhsa-miR-1910-5pであり、miR-2278がhsa-miR-2278であり、miR-2682-3pがhsa-miR-2682-3pであり、miR-3122がhsa-miR-3122であり、miR-3151-5pがhsa-miR-3151-5pであり、miR-3175がhsa-miR-3175であり、miR-4323がhsa-miR-4323であり、miR-4326がhsa-miR-4326であり、miR-4284がhsa-miR-4284であり、miR-3605-3pがhsa-miR-3605-3pであり、miR-3622b-5pがhsa-miR-3622b-5pであり、miR-3646がhsa-miR-3646であり、miR-3158-5pがhsa-miR-3158-5pであり、miR-4722-3pがhsa-miR-4722-3pであり、miR-4728-3pがhsa-miR-4728-3pであり、miR-4747-3pがhsa-miR-4747-3pであり、miR-4436b-5pがhsa-miR-4436b-5pであり、miR-5196-3pがhsa-miR-5196-3pであり、miR-5589-5pがhsa-miR-5589-5pであり、miR-345-3pがhsa-miR-345-3pであり、miR-642b-5pがhsa-miR-642b-5pであり、miR-6716-3pがhsa-miR-6716-3pであり、miR-6511b-3pがhsa-miR-6511b-3pであり、miR-208a-5pがhsa-miR-208a-5pであり、miR-6726-3pがhsa-miR-6726-3pであり、miR-6744-5pがhsa-miR-6744-5pであり、miR-6782-3pがhsa-miR-6782-3pであり、miR-6789-3pがhsa-miR-6789-3pであり、miR-6797-3pがhsa-miR-6797-3pであり、miR-
6800-3pがhsa-miR-6800-3pであり、miR-6806-5pがhsa-miR-6806-5pであり、miR-6824-3pがhsa-miR-6824-3pであり、miR-6837-5pがhsa-miR-6837-5pであり、miR-6846-3pがhsa-miR-6846-3pであり、miR-6858-3pがhsa-miR-6858-3pであり、miR-6859-3pがhsa-miR-6859-3pであり、miR-6861-3pがhsa-miR-6861-3pであり、miR-6880-3pがhsa-miR-6880-3pであり、miR-7111-3pがhsa-miR-7111-3pであり、miR-7152-5pがhsa-miR-7152-5pであり、miR-642a-5pがhsa-miR-642a-5pであり、miR-657がhsa-miR-657であり、miR-1236-3pがhsa-miR-1236-3pであり、miR-764がhsa-miR-764であり、miR-4314がhsa-miR-4314であり、miR-3675-3pがhsa-miR-3675-3pであり、miR-5703がhsa-miR-5703であり、miR-3191-5pがhsa-miR-3191-5pであり、miR-6511a-3pがhsa-miR-6511a-3pであり、miR-6809-3pがhsa-miR-6809-3pであり、miR-6815-5pがhsa-miR-6815-5pであり、miR-6857-3pがhsa-miR-6857-3pであり、miR-6878-3pがhsa-miR-6878-3pであり、miR-371a-5pがhsa-miR-371a-5pであり、miR-766-3pがhsa-miR-766-3pであり、miR-1229-3pがhsa-miR-1229-3pであり、miR-1306-5pがhsa-miR-1306-5pであり、miR-210-5pがhsa-miR-210-5pであり、miR-198がhsa-miR-198であり、miR-485-3pがhsa-miR-485-3pであり、miR-668-3pがhsa-miR-668-3pであり、miR-532-3pがhsa-miR-532-3pであり、miR-877-3pがhsa-miR-877-3pであり、miR-1238-3pがhsa-miR-1238-3pであり、miR-3130-5pがhsa-miR-3130-5pであり、miR-4298がhsa-miR-4298であり、miR-4290がhsa-miR-4290であり、miR-3943がhsa-miR-3943であり、miR-346がhsa-miR-346であり、miR-767-3pがhsa-miR-767-3pであり、miR-516a-5pがhsa-miR-516a-5pであり、miR-769-3pがhsa-miR-769-3pであり、miR-3692-5pがhsa-miR-3692-5pであり、miR-3945がhsa-miR-3945であり、miR-4433a-3pがhsa-miR-4433a-3pであり、miR-4485-3pがhsa-miR-4485-3pであり、miR-6831-5pがhsa-miR-6831-5pであり、miR-519c-5pがhsa-miR-519c-5pであり、miR-551b-5pがhsa-miR-551b-5pであり、miR-1343-3pがhsa-miR-1343-3pであり、miR-4286がhsa-miR-4286であり、miR-4634がhsa-miR-4634であり、miR-4733-3pがhsa-miR-4733-3pであり、miR-6086がhsa-miR-6086であり、miR-30d-5pがhsa-miR-30d-5pであり、miR-30b-3pがhsa-miR-30b-3pであり、miR-92a-3pがhsa-miR-92a-3pであり、miR-371b-5pがhsa-miR-371b-5pであり、miR-486-5pがhsa-miR-486-5pである。
本明細書中で使用する用語は、以下の定義を有する。
また、配列番号1315~1434等で表される遺伝子の名称とmiRBase Accession No.(登録番号)を表1-2に記載した。
本発明の上記定義の認知症検出用の核酸プローブ又はプライマーを使用して、認知症又は認知症の存在又は不存在を検出するための、認知症マーカーとしての主要な標的核酸には、(i)miR-4274、miR-4272、miR-4728-5p、miR-4443、miR-4506、miR-6773-5p、miR-4662a-5p、miR-3184-3p、miR-4281、miR-320d、miR-6729-3p、miR-5192、miR-6853-5p、miR-1234-3p、miR-1233-3p、miR-4539、miR-3914、miR-4738-5p、miR-548au-3p、miR-1539、miR-4720-3p、miR-365b-5p、miR-4486、miR-1227-5p、miR-4667-5p、miR-6088、miR-6820-5p、miR-4505、miR-548q、miR-4658、miR-450a-5p、miR-1260b、miR-3677-5p、miR-6777-3p、miR-6826-3p、miR-6832-3p、miR-4725-3p、miR-7161-3p、miR-2277-5p、miR-7110-3p、miR-4312、miR-4461、miR-6766-5p、miR-1266-3p、miR-6729-5p、miR-526b-3p、miR-519e-5p、miR-512-5p、miR-5088-5p、miR-1909-3p、miR-6511a-5p、miR-4734、miR-936、miR-1249-3p、miR-6777-5p、miR-4487、miR-3155a、miR-563、miR-4741、miR-6788-5p、miR-4433b-5p、miR-323a-5p、miR-6811-5p、miR-6721-5p、miR-5004-5p、miR-6509-3p、miR-648、miR-3917、miR-6087、miR-1470、miR-586、miR-3150a-5p、miR-105-3p、miR-7973、miR-1914-5p、miR-4749-3p、miR-15b-5p、miR-1289、miR-4433a-5p、miR-3666、miR-3186-3p、miR-4725-5p、miR-4488、miR-4474-3p、miR-6731-3p、miR-4640-3p、miR-202-5p、miR-6816-5p、miR-638、miR-6821-5p、miR-1247-3p、miR-6765-5p、miR-6800-5p、miR-3928-3p、miR-3940-5p、miR-3960、miR-6775-5p、miR-3178、miR-1202、miR-6790-5p、miR-4731-3p、miR-2681-3p、miR-6758-5p、miR-8072、miR-518d-3p、miR-3606-3p、miR-4800-5p、miR-1292-3p、miR-6784-3p、miR-4450、miR-6132、miR-4716-5p、miR-6860、miR-1268b、miR-378d、miR-4701-5p、miR-4329、miR-185-3p、miR-552-3p、miR-1273g-5p、miR-6769b-3p、miR-520a-3p、miR-4524b-5p、miR-4291、miR-6734-3p、miR-143-5p、miR-939-3p、miR-6889-3p、miR-6842-3p、miR-4511、miR-4318、miR-4653-5p、miR-6867-3p、miR-133b、miR-3196、miR-193b-3p、miR-3162-3p、miR-6819-3p、miR-1908-3p、miR-6786-5p、miR-3648、miR-4513、miR-3652、miR-4640-5p、miR-6871-5p、miR-7845-5p、miR-3138、miR-6884-5p、miR-4653-3p、miR-636、miR-4652-3p、miR-6823-5p、miR-4502、miR-7113-5p、miR-8087、miR-7154-3p、miR-5189-5p、miR-1253、miR-518c-5p、miR-7151-5p、miR-3614-3p、miR-4727-5p、miR-3682-5p、miR-5090、miR-337-3p、miR-488-5p、miR-100-5p、miR-4520-3p、miR-373-3p、miR-6499-5p、miR-3909、miR-32-5p、miR-302a-3p、miR-4686、miR-4659a-3p、miR-4287、miR-1301-5p、miR-593-3p、miR-517a-3p、miR-517b-3p、miR-142-3p、miR-1185-2-3p、miR-602、miR-527、miR-518a-5p、miR-4682、miR-28-5p、miR-4252、miR-452-5p、miR-525-5p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、miR-7114-5p、miR-516a-5p、miR-769-3p、miR-3692-5p、miR-3945、miR-4433a-3p、miR-4485-3p、miR-6831-5p、miR-519c-5p、miR-551b-5p、miR-1343-3p、miR-4286、miR-4634、miR-4733-3p、及びmiR-6086からなる群から選択される少なくとも1つのmiRNAが含まれる。さらにこれらのmiRNA(i)と組み合わせることができる他の認知症マーカー、すなわち、(ii)miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、miR-3665、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p及びmiR-486-5pからなる群から選択される1個、2個又は3個以上、10個以上、好ましくは3個~30個のmiRNAも標的核酸として好ましく用いることができる。上記miRNA(i)~(ii)に加えて、又は上記miRNA(i)~(ii)とは別に、(iii)miR-4728-5p、miR-3184-3p、miR-1233-3p、miR-6088、miR-6777-3p、miR-7110-3p、miR-936、miR-6087、miR-1202、miR-4731-3p、miR-4800-5p、miR-6784-3p、miR-4716-5p、miR-6734-3p、miR-6889-3p、miR-6867-3p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-3184-5p、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-
5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p及びmiR-6878-3pからなる群から選択される1個、2個又は3個以上、10個以上、好ましくは3個~110個のmiRNAも標的核酸として好ましく用いることができる。上記miRNA(i)~(iii)と組み合わせることができる他の認知症マーカーとして、(iv)miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346及びmiR-767-3pからなる群から選択される1個、2個又は3個以上、10個以上、好ましくは3個~110個のmiRNAも標的核酸として好ましく用いることができる。
486-5p)、その同族体、その転写産物、及びその変異体又は誘導体が含まれる。ここで、遺伝子、同族体、転写産物、変異体及び誘導体は、上記定義のとおりである。
本発明において、認知症を検出するための、あるいは認知症を診断するために使用可能な核酸プローブ又はプライマーは、認知症の標的核酸としての、ヒト由来のmiR-4274、miR-4272、miR-4728-5p、miR-4443、miR-4506、miR-6773-5p、miR-4662a-5p、miR-3184-3p、miR-4281、miR-320d、miR-6729-3p、miR-5192、miR-6853-5p、miR-1234-3p、miR-1233-3p、miR-4539、miR-3914、miR-4738-5p、miR-548au-3p、miR-1539、miR-4720-3p、miR-365b-5p、miR-4486、miR-1227-5p、miR-4667-5p、miR-6088、miR-6820-5p、miR-4505、miR-548q、miR-4658、miR-450a-5p、miR-1260b、miR-3677-5p、miR-6777-3p、miR-6826-3p、miR-6832-3p、miR-4725-3p、miR-7161-3p、miR-2277-5p、miR-7110-3p、miR-4312、miR-4461、miR-6766-5p、miR-1266-3p、miR-6729-5p、miR-526b-3p、miR-519e-5p、miR-512-5p、miR-5088-5p、miR-1909-3p、miR-6511a-5p、miR-4734、miR-936、miR-1249-3p、miR-6777-5p、miR-4487、miR-3155a、miR-563、miR-4741、miR-6788-5p、miR-4433b-5p、miR-323a-5p、miR-6811-5p、miR-6721-5p、miR-5004-5p、miR-6509-3p、miR-648、miR-3917、miR-6087、miR-1470、miR-586、miR-3150a-5p、miR-105-3p、miR-7973、miR-1914-5p、miR-4749-3p、miR-15b-5p、miR-1289、miR-4433a-5p、miR-3666、miR-3186-3p、miR-4725-5p、miR-4488、miR-4474-3p、miR-6731-3p、miR-4640-3p、miR-202-5p、miR-6816-5p、miR-638、miR-6821-5p、miR-1247-3p、miR-6765-5p、miR-6800-5p、miR-3928-3p、miR-3940-5p、miR-3960、miR-6775-5p、miR-3178、miR-1202、miR-6790-5p、miR-4731-3p、miR-2681-3p、miR-6758-5p、miR-8072、miR-518d-3p、miR-3606-3p、miR-4800-5p、miR-1292-3p、miR-6784-3p、miR-4450、miR-6132、miR-4716-5p、miR-6860、miR-1268b、miR-378d、miR-4701-5p、miR-4329、miR-185-3p、miR-552-3p、miR-1273g-5p、miR-6769b-3p、miR-520a-3p、miR-4524b-5p、miR-4291、miR-6734-3p、miR-143-5p、miR-939-3p、miR-6889-3p、miR-6842-3p、miR-4511、miR-4318、miR-4653-5p、miR-6867-3p、miR-133b、miR-3196、miR-193b-3p、miR-3162-3p、miR-6819-3p、miR-1908-3p、miR-6786-5p、miR-3648、miR-4513、miR-3652、miR-4640-5p、miR-6871-5p、miR-7845-5p、miR-3138、miR-6884-5p、miR-4653-3p、miR-636、miR-4652-3p、miR-6823-5p、miR-4502、miR-7113-5p、miR-8087、miR-7154-3p、miR-5189-5p、miR-1253、miR-518c-5p、miR-7151-5p、miR-3614-3p、miR-4727-5p、miR-3682-5p、miR-5090、miR-337-3p、miR-488-5p、miR-100-5p、miR-4520-3p、miR-373-3p、miR-6499-5p、miR-3909、miR-32-5p、miR-302a-3p、miR-4686、miR-4659a-3p、miR-4287、miR-1301-5p、miR-593-3p、miR-517a-3p、miR-517b-3p、miR-142-3p、miR-1185-2-3p、miR-602、miR-527、miR-518a-5p、miR-4682、miR-28-5p、miR-4252、miR-452-5p、miR-525-5p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p及びmiR-7114-5p、miR-516a-5p、miR-769-3p、miR-3692-5p、miR-3945、miR-4433a-3p、miR-4485-3p、miR-6831-5p、miR-519c-5p、miR-551b-5p、miR-1343-3p、miR-4286、miR-4634、miR-4733-3p、miR-6086、miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p及びmiR-3665、、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p、miR-486-5pmiR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、miR-6878-3p、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346又はmiR-767-3p、あるいはそれらの組み合わせ、それらの同族体、それらの転写産物、あるいはそれらの変異体
又は誘導体の存在、発現量又は存在量を定性的及び/又は定量的に測定することを可能にする。
(a)配列番号1~210、374、1315~1350及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、並びに、
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド。
(f)配列番号211~249及び1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、(g)配列番号211~249及び1351~1356及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249及び1351~1356及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249及び1351~1356及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、並びに、
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件でハイブリダイズするポリヌクレオチド。
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド。
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド。
(u)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(v)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列を含むポリヌクレオチド、(w)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(x)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(y)前記(u)~(x)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド。
(a)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、並びに、
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド。
一実施形態において、本発明で使用可能な核酸プローブ又はプライマーは、上記のポリヌクレオチド(a)~(e)のいずれかから選択される少なくとも1つのポリヌクレオチドの他に、下記の(f)~(j)のいずれかに示すポリヌクレオチドを、さらに含むことができる:
(f)配列番号211~212及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~212及び1351~1356のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~212及び1351~1356のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、(i)配列番号211~212及び1351~1356のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列を含むポリヌクレオチド、並びに、
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件でハイブリダイズするポリヌクレオチド。
98、hsa-mir-4290、hsa-mir-3943、hsa-mir-346、hsa-mir-767、hsa-mir-516a-1、hsa-mir-769、hsa-mir-3692、hsa-mir-3945、hsa-mir-4433a、hsa-mir-4485、hsa-mir-6831、hsa-mir-519c、hsa-mir-551b、hsa-mir-1343、hsa-mir-4286、hsa-mir-4634、hsa-mir-4733、hsa-mir-6086、hsa-mir-30d、hsa-mir-30b、hsa-mir-92a-1、hsa-mir-371b、hsa-mir-486-1、配列番号3のisomiR配列1、配列番号3のisomiR配列2、配列番号4のisomiR配列1、配列番号4のisomiR配列2、配列番号5のisomiR配列1、配列番号5のisomiR配列2、配列番号6のisomiR配列1、配列番号6のisomiR配列2、配列番号7のisomiR配列1、配列番号8のisomiR配列1、配列番号10のisomiR配列1、配列番号10のisomiR配列2、配列番号11のisomiR配列1、配列番号12のisomiR配列1、配列番号13のisomiR配列1、配列番号15のisomiR配列1、配列番号15のisomiR配列2、配列番号16のisomiR配列1、配列番号17のisomiR配列1、配列番号19のisomiR配列1、配列番号22のisomiR配列1、配列番号22のisomiR配列2、配列番号23のisomiR配列1、配列番号25のisomiR配列1、配列番号25のisomiR配列2、配列番号26のisomiR配列1、配列番号26のisomiR配列2、配列番号28のisomiR配列1、配列番号29のisomiR配列1、配列番号29のisomiR配列2、配列番号30のisomiR配列1、配列番号31のisomiR配列1、配列番号31のisomiR配列2、配列番号32のisomiR配列1、配列番号32のisomiR配列2、配列番号33のisomiR配列1、配列番号34のisomiR配列1、配列番号35のisomiR配列1、配列番号36のisomiR配列1、配列番号37のisomiR配列1、配列番号37のisomiR配列2、配列番号39のisomiR配列1、配列番号39のisomiR配列2、配列番号40のisomiR配列1、配列番号40のisomiR配列2、配列番号41のisomiR配列1、配列番号44のisomiR配列1、配列番号47のisomiR配列1、配列番号48のisomiR配列1、配列番号49のisomiR配列1、配列番号49のisomiR配列2、配列番号50のisomiR配列1、配列番号50のisomiR配列2、配列番号51のisomiR配列1、配列番号51のisomiR配列2、配列番号52のisomiR配列1、配列番号54のisomiR配列1、配列番号54のisomiR配列2、配列番号56のisomiR配列1、配列番号56のisomiR配列2、配列番号57のisomiR配列1、配列番号57のisomiR配列2、配列番号59のisomiR配列1、配列番号59のisomiR配列2、配列番号60のisomiR配列1、配列番号60のisomiR配列2、配列番号61のisomiR配列1、配列番号61のisomiR配列2、配列番号62のisomiR配列1、配列番号62のisomiR配列2、配列番号63のisomiR配列1、配列番号63のisomiR配列2、配列番号64のisomiR配列1、配列番号64のisomiR配列2、配列番号65のisomiR配列1、配列番号66のisomiR配列1、配列番号67のisomiR配列1、配列番号68のisomiR配列1、配列番号68のisomiR配列2、配列番号69のisomiR配列1、配列番号69のisomiR配列2、配列番号70のisomiR配列1、配列番号71のisomiR配列1、配列番号72のisomiR配列1、配列番号72のisomiR配列2、配列番号73のisomiR配列1、配列番号73のisomiR配列2、配列番号75のisomiR配列1、配列番号77のisomiR配列1、配列番号77のisomiR配列2、配列番号78のisomiR配列1、配列番号79のisomiR配列1、配列番号81のisomiR配列1、配列番号81のisomiR配列2、配列番号82のisomiR配列1、配列番号83のisomiR配列1、配列番号83のisomiR配列2、配列番号84のisomiR配列1、配列番号85のisomiR配列1、配列番号86のisomiR配列1、配列番号87のisomiR配列1、配列番号87のisomiR配列2、配列番号89のisomiR配列1、配列番号89のisomiR配列2、配列番号91のisomiR配列1、配列番号91のisomiR配列2、配列番号94のisomiR配列1、配列番号94のisomiR配列2、配列番号95のisomiR配列1、配列番号95のisomiR配列2、配列番号96のisomiR配列1、配列番号96のisomiR配列2、配列番号98のisomiR配列1、配列番号98のisomiR配列2、配列番号99のisomiR配列1、配列番号100のisomiR配列1、配列番号101のisomiR配列1、配列番号102のisomiR配列1、配列番号103のisomiR配列1、配列番号103のisomiR配列2、配列番号105のisomiR配列1、配列番号107のisomiR配列1、配列番号109のisomiR配列1、配列番号111のisomiR配列1、配列番号112のisomiR配列1、配列番号112のisomiR配列2、配列番号113のisomiR配列1、配列番号114のisomiR配列1、配列番号114のisomiR配列2、配列番号115のisomiR配列1、配列番号115のisomiR配列2、配列番号116のisomiR配列1、配列番号116のisomiR配列2、配列番号118のisomiR配列1、配列番号118のisomiR配列2、配列番号119のisomiR配列1、配列番号121のisomiR配列1、配列番号122のisomiR配列1、配列番号125のisomiR配列1、配列番号126のisomiR配列1、配列番号126のisomiR配列2、配列番号127のisomiR配列1、配列番号127のisomiR配列2、配列番号128のisomiR配列1、配列番号129のisomiR配列1、配列番号130のisomiR配列1、配列番号130のisomiR配列2、配列番号133のisomiR配列1、配列番号134のisomiR配列1、配列番号134のisomiR配列2、配列番号135のisomiR配列1、配列番号135のisomiR配列2、配列番号136のisomiR配列1、配列番号136のisomiR配列2、配列番号137のisomiR配列1、配列番号138のisomiR配列1、配列番号139のisomiR配列1、配列番号139のisomiR配列2、配列番号141のisomiR配列1、配列番号141のisomiR配列2、配列番号142のisomiR配列1、配列番号142のisomiR配列2、配列番号143のisomiR配列1、配列番号143のisomiR配列2、配列番号144のisomiR配列1、配列番号144のisomiR配列2、配列番号145のisomiR配列1、配列番号145のisomiR配列2、配列番号147のisomiR配列1、配列番号147のisomiR配列2、配列番号148のisomiR配列1、配列番号148のisomiR配列2、配列番号149のisomiR配列1、配列番号149のisomiR配列2、配列番号150のisomiR配列1、配列番号150のisomiR配列2、配列番号151のisomiR配列1、配列番号151のisomiR配列2、配列番号152のisomiR配列1、配列番号152のisomiR配列2、配列番号153のisomiR配列1、配列番号153のisomiR配列2、配列番号154のisomiR配列1、配列番号154のisomiR配列2、配列番号157のisomiR配列1、配列番号157のisomiR配列2、配列番号158のisomiR配列1、配列番号159のisomiR配列1、配列番号161のisomiR配列1、配列番号161のisomiR配列2、配列番号162のisomiR配列1、配列番号163のisomiR配列1、配列番号163のisomiR配列2、配列番号164のisomiR配列1、配列番号164のisomiR配列2、配列番号165のisomiR配列1、配列番号165のisomiR配列2、配列番号166のisomiR配列1、配列番号167のisomiR配列1、配列番号167のisomiR配列2、配列番号168のisomiR配列1、配列番号168のisomiR配列2、配列番号169のisomiR配列1、配列番号170のisomiR配列1、配列番号170のisomiR配列2、配列番号171のisomiR配列1、配列番号171のisomiR配列2、配列番号172のisomiR配列1、配列番号172のisomiR配列2、配列番号173のisomiR配列1、配列番号173のisomiR配列2、配列番号175のisomiR配列1、配列番号175のisomiR配列2、配列番号177のisomiR配列1、配列番号177のisomiR配列2、配列番号179のisomiR配列1、配列番号179のisomiR配列2、配列番号180のisomiR配列1、配列番号180のisomiR配列2、配列番号181のisomiR配列1、配列番号181のisomiR配列2、配列番号182のisomiR配列1、配列番号182のisomiR配列2、配列番号185のisomiR配列1、配列番号187のisomiR配列1、配列番号187のisomiR配列2、配列番号189のisomiR配列1、配列番号189のisomiR配列2、配列番号190のisomiR配列1、配列番号191のisomiR配列1、配列番号191のisomiR配列2、配列番号192のisomiR配列1、配列番号194のisomiR配列1、配列番号194のisomiR配列2、配列番号195のisomiR配列1、配列番号195のisomiR配列2、配列番号199のisomiR配列1、配列番号199のisomiR配列2、配列番号202のisomiR配列1、配列番号202のisomiR配列2、配列番号203のisomiR配列1、配列番号205のisomiR配列1、配列番号205のisomiR配列2、配列番号206のisomiR配列1、配列番号206のisomiR配列2、配列番号208のisomiR配列1、配列番号208のisomiR配列2、配列番号209のisomiR配列1、配列番号209のisomiR配列2、配列番号213のisomiR配列1、配列番号213のisomiR配列2、配列番号214のisomiR配列1、配列番号214のisomiR配列2、配列番号215のisomiR配列1、配列番号215のisomiR配列2、配列番号216のisomiR配列1、配列番号216のisomiR配列2、配列番号217のisomiR配列1、配列番号217のisomiR配列2、配列番号218のisomiR配列1、配列番号218のisomiR配列2、配列番号219のisomiR配列1、配列番号219のisomiR配列2、配列番号220のisomiR配列1、配列番号220のisomiR配列2、配列番号221のisomiR配列1、配列番号221のisomiR配列2、配列番号222のisomiR配列1、配列番号222のisomiR配列2、配列番号223のisomiR配列1、配列番号223のisomiR配列2、配列番号224のisomiR配列1、配列番号224のisomiR配列2、配列番号225のisomiR配列1、配列番号225のisom
iR配列2、配列番号226のisomiR配列1、配列番号226のisomiR配列2、配列番号227のisomiR配列1、配列番号227のisomiR配列2、配列番号228のisomiR配列1、配列番号228のisomiR配列2、配列番号229のisomiR配列1、配列番号229のisomiR配列2、配列番号230のisomiR配列1、配列番号231のisomiR配列1、配列番号231のisomiR配列2、配列番号232のisomiR配列1、配列番号232のisomiR配列2、配列番号233のisomiR配列1、配列番号233のisomiR配列2、配列番号234のisomiR配列1、配列番号234のisomiR配列2、配列番号235のisomiR配列1、配列番号235のisomiR配列2、配列番号236のisomiR配列1、配列番号236のisomiR配列2、配列番号237のisomiR配列1、配列番号237のisomiR配列2、配列番号238のisomiR配列1、配列番号238のisomiR配列2、配列番号239のisomiR配列1、配列番号239のisomiR配列2、配列番号241のisomiR配列1、配列番号241のisomiR配列2、配列番号242のisomiR配列1、配列番号242のisomiR配列2、配列番号243のisomiR配列1、配列番号243のisomiR配列2、配列番号244のisomiR配列1、配列番号244のisomiR配列2、配列番号245のisomiR配列1、配列番号245のisomiR配列2、配列番号246のisomiR配列1、配列番号246のisomiR配列2、配列番号247のisomiR配列1、配列番号247のisomiR配列2、配列番号248のisomiR配列1、配列番号248のisomiR配列2、配列番号249のisomiR配列1、配列番号249のisomiR配列2、配列番号251のisomiR配列1、配列番号251のisomiR配列2、配列番号252のisomiR配列1、配列番号252のisomiR配列2、配列番号253のisomiR配列1、配列番号253のisomiR配列2、配列番号255のisomiR配列1、配列番号256のisomiR配列1、配列番号256のisomiR配列2、配列番号257のisomiR配列1、配列番号257のisomiR配列2、配列番号259のisomiR配列1、配列番号259のisomiR配列2、配列番号260のisomiR配列1、配列番号260のisomiR配列2、配列番号261のisomiR配列1、配列番号261のisomiR配列2、配列番号262のisomiR配列1、配列番号262のisomiR配列2、配列番号263のisomiR配列1、配列番号263のisomiR配列2、配列番号264のisomiR配列1、配列番号264のisomiR配列2、配列番号265のisomiR配列1、配列番号268のisomiR配列1、配列番号269のisomiR配列1、配列番号269のisomiR配列2、配列番号270のisomiR配列1、配列番号270のisomiR配列2、配列番号271のisomiR配列1、配列番号271のisomiR配列2、配列番号272のisomiR配列1、配列番号272のisomiR配列2、配列番号273のisomiR配列1、配列番号273のisomiR配列2、配列番号274のisomiR配列1、配列番号274のisomiR配列2、配列番号275のisomiR配列1、配列番号275のisomiR配列2、配列番号276のisomiR配列1、配列番号277のisomiR配列1、配列番号277のisomiR配列2、配列番号278のisomiR配列1、配列番号278のisomiR配列2、配列番号279のisomiR配列1、配列番号280のisomiR配列1、配列番号280のisomiR配列2、配列番号281のisomiR配列1、配列番号281のisomiR配列2、配列番号282のisomiR配列1、配列番号282のisomiR配列2、配列番号283のisomiR配列1、配列番号283のisomiR配列2、配列番号284のisomiR配列1、配列番号284のisomiR配列2、配列番号286のisomiR配列1、配列番号286のisomiR配列2、配列番号287のisomiR配列1、配列番号287のisomiR配列2、配列番号288のisomiR配列1、配列番号288のisomiR配列2、配列番号289のisomiR配列1、配列番号289のisomiR配列2、配列番号290のisomiR配列1、配列番号291のisomiR配列1、配列番号291のisomiR配列2、配列番号292のisomiR配列1、配列番号293のisomiR配列1、配列番号293のisomiR配列2、配列番号295のisomiR配列1、配列番号295のisomiR配列2、配列番号296のisomiR配列1、配列番号296のisomiR配列2、配列番号297のisomiR配列1、配列番号297のisomiR配列2、配列番号298のisomiR配列1、配列番号299のisomiR配列1、配列番号299のisomiR配列2、配列番号300のisomiR配列1、配列番号300のisomiR配列2、配列番号301のisomiR配列1、配列番号302のisomiR配列1、配列番号302のisomiR配列2、配列番号303のisomiR配列1、配列番号304のisomiR配列1、配列番号304のisomiR配列2、配列番号305のisomiR配列1、配列番号305のisomiR配列2、配列番号306のisomiR配列1、配列番号306のisomiR配列2、配列番号307のisomiR配列1、配列番号308のisomiR配列1、配列番号308のisomiR配列2、配列番号309のisomiR配列1、配列番号310のisomiR配列1、配列番号311のisomiR配列1、配列番号311のisomiR配列2、配列番号312のisomiR配列1、配列番号313のisomiR配列1、配列番号313のisomiR配列2、配列番号314のisomiR配列1、配列番号314のisomiR配列2、配列番号315のisomiR配列1、配列番号316のisomiR配列1、配列番号316のisomiR配列2、配列番号317のisomiR配列1、配列番号317のisomiR配列2、配列番号320のisomiR配列1、配列番号320のisomiR配列2、配列番号321のisomiR配列1、配列番号321のisomiR配列2、配列番号322のisomiR配列1、配列番号322のisomiR配列2、配列番号323のisomiR配列1、配列番号323のisomiR配列2、配列番号324のisomiR配列1、配列番号324のisomiR配列2、配列番号325のisomiR配列1、配列番号325のisomiR配列2、配列番号326のisomiR配列1、配列番号326のisomiR配列2、配列番号327のisomiR配列1、配列番号328のisomiR配列1、配列番号328のisomiR配列2、配列番号329のisomiR配列1、配列番号329のisomiR配列2、配列番号330のisomiR配列1、配列番号330のisomiR配列2、配列番号331のisomiR配列1、配列番号332のisomiR配列1、配列番号333のisomiR配列1、配列番号333のisomiR配列2、配列番号335のisomiR配列1、配列番号335のisomiR配列2、配列番号338のisomiR配列1、配列番号338のisomiR配列2、配列番号340のisomiR配列1、配列番号340のisomiR配列2、配列番号341のisomiR配列1、配列番号341のisomiR配列2、配列番号342のisomiR配列1、配列番号342のisomiR配列2、配列番号343のisomiR配列1、配列番号343のisomiR配列2、配列番号345のisomiR配列1、配列番号345のisomiR配列2、配列番号347のisomiR配列1、配列番号347のisomiR配列2、配列番号348のisomiR配列1、配列番号348のisomiR配列2、配列番号349のisomiR配列1、配列番号349のisomiR配列2、配列番号350のisomiR配列1、配列番号352のisomiR配列1、配列番号352のisomiR配列2、配列番号353のisomiR配列1、配列番号353のisomiR配列2、配列番号354のisomiR配列1、配列番号355のisomiR配列1、配列番号355のisomiR配列2、配列番号356のisomiR配列1、配列番号356のisomiR配列2、配列番号357のisomiR配列1、配列番号357のisomiR配列2、配列番号359のisomiR配列1、配列番号359のisomiR配列2、配列番号361のisomiR配列1、配列番号361のisomiR配列2、配列番号362のisomiR配列1、配列番号363のisomiR配列1、配列番号363のisomiR配列2、配列番号367のisomiR配列1、配列番号367のisomiR配列2、配列番号368のisomiR配列1、配列番号368のisomiR配列2、配列番号369のisomiR配列1、配列番号369のisomiR配列2、配列番号371のisomiR配列1、配列番号371のisomiR配列2、配列番号372のisomiR配列1、配列番号372のisomiR配列2、配列番号373のisomiR配列1、配列番号374のisomiR配列1、配列番号374のisomiR配列2、配列番号375のisomiR配列1、配列番号375のisomiR配列2、配列番号376のisomiR配列1、配列番号376のisomiR配列2、配列番号377のisomiR配列1、配列番号377のisomiR配列2、配列番号378のisomiR配列1、配列番号378のisomiR配列2、配列番号379のisomiR配列1、配列番号379のisomiR配列2、配列番号380のisomiR配列1、配列番号380のisomiR配列2、配列番号381のisomiR配列1、配列番号381のisomiR配列2、配列番号382のisomiR配列1、配列番号382のisomiR配列2、配列番号383のisomiR配列1、配列番号383のisomiR配列2、配列番号385のisomiR配列1、配列番号385のisomiR配列2、配列番号386のisomiR配列1、配列番号386のisomiR配列2、配列番号388のisomiR配列1、配列番号388のisomiR配列2、配列番号389のisomiR配列1、配列番号389のisomiR配列2、配列番号390のisomiR配列1、配列番号390のisomiR配列2、配列番号1435のisomiR配列1、配列番号1435のisomiR配列2、配列番号1436のisomiR配列1、配列番号1436のisomiR配列2、配列番号1438のisomiR配列1、配列番号1438のisomiR配列2、配列番号1439のisomiR配列1、配列番号1439のisomiR配列2、配列番号1440のisomiR配列1、配列番号1440のisomiR配列2、配列番号1441のisomiR配列1、配列番号1441のisomiR配列2、配列番号1446のisomiR配列1、配列番号1446のisomiR配列2、配列番号1448のisomiR配列1、配列番号1448のisomiR配列2、配列番号1449のisomiR配列1、配列番号1449のisomiR配列2、配列番号1451のisomiR配列1、配列番号1451のisomiR配列2、配列番号1452のisomiR配列1、配列番号1452のisomiR配列2、配列番号1455のisomiR配列1、配列番号1458のisomiR配列1、配列番号1458のisomiR配列2、配列番号1460のisomi
R配列1、配列番号1460のisomiR配列2、配列番号1461のisomiR配列1、配列番号1461のisomiR配列2、配列番号1462のisomiR配列1、配列番号1462のisomiR配列2、配列番号1463のisomiR配列1、配列番号1463のisomiR配列2についても同様に公知であり、前述のようにその取得方法も知られている。このため、この遺伝子をクローニングすることによって、本発明で使用可能な核酸プローブ又はプライマーとしてのポリヌクレオチドを作製することができる。
本発明は、認知症マーカーである標的核酸を測定するための、本発明において核酸プローブ又はプライマーとして使用可能なポリヌクレオチド(これには、変異体、断片、又は誘導体を含みうる。)の1つ又は複数を含む認知症検出用キット又はデバイスを提供する。
群A:
miR-4274、miR-4272、miR-4728-5p、miR-4443、miR-4506、miR-6773-5p、miR-4662a-5p、miR-3184-3p、miR-4281、miR-320d、miR-6729-3p、miR-5192、miR-6853-5p、miR-1234-3p、miR-1233-3p、miR-4539、miR-3914、miR-4738-5p、miR-548au-3p、miR-1539、miR-4720-3p、miR-365b-5p、miR-4486、miR-1227-5p、miR-4667-5p、miR-6088、miR-6820-5p、miR-4505、miR-548q、miR-4658、miR-450a-5p、miR-1260b、miR-3677-5p、miR-6777-3p、miR-6826-3p、miR-6832-3p、miR-4725-3p、miR-7161-3p、miR-2277-5p、miR-7110-3p、miR-4312、miR-4461、miR-6766-5p、miR-1266-3p、miR-6729-5p、miR-526b-3p、miR-519e-5p、miR-512-5p、miR-5088-5p、miR-1909-3p、miR-6511a-5p、miR-4734、miR-936、miR-1249-3p、miR-6777-5p、miR-4487、miR-3155a、miR-563、miR-4741、miR-6788-5p、miR-4433b-5p、miR-323a-5p、miR-6811-5p、miR-6721-5p、miR-5004-5p、miR-6509-3p、miR-648、miR-3917、miR-6087、miR-1470、miR-586、miR-3150a-5p、miR-105-3p、miR-7973、miR-1914-5p、miR-4749-3p、miR-15b-5p、miR-1289、miR-4433a-5p、miR-3666、miR-3186-3p、miR-4725-5p、miR-4488、miR-4474-3p、miR-6731-3p、miR-4640-3p、miR-202-5p、miR-6816-5p、miR-638、miR-6821-5p、miR-1247-3p、miR-6765-5p、miR-6800-5p、miR-3928-3p、miR-3940-5p、miR-3960、miR-6775-5p、miR-3178、miR-1202、miR-6790-5p、miR-4731-3p、miR-2681-3p、miR-6758-5p、miR-8072、miR-518d-3p、miR-3606-3p、miR-4800-5p、miR-1292-3p、miR-6784-3p、miR-4450、miR-6132、miR-4716-5p、miR-6860、miR-1268b、miR-378d、miR-4701-5p、miR-4329、miR-185-3p、miR-552-3p、miR-1273g-5p、miR-6769b-3p、miR-520a-3p、miR-4524b-5p、miR-4291、miR-6734-3p、miR-143-5p、miR-939-3p、miR-6889-3p、miR-6842-3p、miR-4511、miR-4318、miR-4653-5p、miR-6867-3p、miR-133b、miR-3196、miR-193b-3p、miR-3162-3p、miR-6819-3p、miR-1908-3p、miR-6786-5p、miR-3648、miR-4513、miR-3652、miR-4640-5p、miR-6871-5p、miR-7845-5p、miR-3138、miR-6884-5p、miR-4653-3p、miR-636、miR-4652-3p、miR-6823-5p、miR-4502、miR-7113-5p、miR-8087、miR-7154-3p、miR-5189-5p、miR-1253、miR-518c-5p、miR-7151-5p、miR-3614-3p、miR-4727-5p、miR-3682-5p、miR-5090、miR-337-3p、miR-488-5p、miR-100-5p、miR-4520-3p、miR-373-3p、miR-6499-5p、miR-3909、miR-32-5p、miR-302a-3p、miR-4686、miR-4659a-3p、miR-4287、miR-1301-5p、miR-593-3p、miR-517a-3p、miR-517b-3p、miR-142-3p、miR-1185-2-3p、miR-602、miR-527、miR-518a-5p、miR-4682、miR-28-5p、miR-4252、miR-452-5p、miR-525-5p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p及びmiR-7114-5p、miR-516a-5p、miR-769-3p、miR-3692-5p、miR-3945、miR-4433a-3p、miR-4485-3p、miR-6831-5p、miR-519c-5p、miR-551b-5p、miR-1343-3p、miR-4286、miR-4634、miR-4733-3p、及びmiR-6086
群B:
miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p及びmiR-3665、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p及びmiR-486-5p
群C:
miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、miR-6878-3p
群D:
miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、miR-767-3p
群E:
miR-4728-5p、miR-3184-3p、miR-1233-3p、miR-6088、miR-6777-3p、miR-7110-3p、miR-936、miR-6087、miR-1202、miR-4731-3p、miR-4800-5p、miR-6784-3p、miR-4716-5p、miR-6734-3p、miR-6889-3p、miR-6867-3p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-3184-5p、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、miR-6878-3p、miR-371a-5pからなる群から選択される1以上のポリヌクレオチド
(1)配列番号1~210のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(2)配列番号211~249のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(3)配列番号250~374のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(4)配列番号375~390のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(5)配列番号391~782のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(6)配列番号783~1314のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(7)配列番号1315~1434のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(8)配列番号1434~1505のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
本発明においてアルツハイマー型認知症患者を、非認知症被検者と判別するためのキット又はデバイスにおける標的核酸の組合せとしては、表1―1に示されるポリヌクレオチド(但し、配列番号1~210及び250~374で表される塩基配列からなるポリヌクレオチドの少なくとも1個を含む。)を2個以上、好ましくは3個~110個組み合わせることが望ましい。具体的には、配列番号1~23、26、34、40、47、49、54、63、72、77、78、83、87、90、91、99、101、104、133、145、146、152~156、191、192及び194、200、206、212、214、215、250~316、375~378に表される塩基配列からなるポリヌクレオチドのいずれか2個以上を含む組み合わせが挙げられ、好ましくは配列番号1~13、15、16、18~20、23、26、49、72、77、83、101、152、153、155、156、192及び194、200、214、215に表される塩基配列からなるポリヌクレオチドのいずれか2個以上を含む組み合わせが挙げられる。
群A’:
miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、miR-7114-5p
群B’:
miR-1225-3p、miR-3184-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、miR-3665
(1)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(2)配列番号211~212及び1351~1356のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(3)配列番号398、490、591、593~609、1357~1399)のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
(4)配列番号1015~1017、1019~1024、1026~1031、1285~1286、及び1400~1434のいずれかで表される塩基配列においてuがtである塩基配列又はその相補的配列において、15以上の連続した塩基配列を含むポリヌクレオチド。
本発明は、検体中の「3.認知症検出用キット又はデバイス」に記載の、(場合により群B~群Dから選択される標的遺伝子と組み合わされ得る)群Aから選択される標的遺伝子、又は(場合により群A、群B又は群Dから選択される標的遺伝子と組み合わされ得る)群Eから選択される標的遺伝子を含む遺伝子の1個以上、2個以上、3個以上、10個以上、好ましくは3個~30個、3個~110個の発現量をin vitroで測定し、該測定された発現量(及び任意に同様に測定された健常者の対照発現量)を用いて被験体が認知症に罹患しているか否かをin vitroで評価することを含む、認知症の検出方法に関する。本方法において、例えば、認知症の罹患が疑われる被験体と非認知症被検者から採取した血液、血清、血漿等の検体について、検体中の上記遺伝子の発現量と非認知症被検者における対照発現量とを用いて、例えば、両発現量を比較して当該検体中の標的核酸の発現量に差がある場合、被験体が認知症に罹患していると評価することができる。
一実施形態において、認知症の罹患が疑われる被験体の血液、血清、血漿、尿等の検体中の、配列番号194~210、374、及び1315~1350の少なくとも1つで表される塩基配列、並びに場合により配列番号211~212及び1351~1356の1つ以上で表される塩基配列からなるポリヌクレオチドの発現量が、認知症に罹患していない被験者の血液、血清、血漿、尿等の検体中のそれらの発現量と比べて統計学的に有意に高い場合、当該被験体は認知症に罹患していると評価することができる。
(a)被験体由来の検体を、in vitroで、本発明のキット又はデバイス中のポリヌクレオチドと接触させるステップ、
(b)検体中の標的核酸の発現量を、上記ポリヌクレオチドを核酸プローブ又はプライマーとして用いて測定するステップ、
(c)(b)の結果をもとに、当該被験体中の認知症(変異タンパク質)の存在又は不存在を評価するステップ、
を含むことができる。
miR-3614-3pがhsa-miR-3614-3pであり、miR-4727-5pがhsa-miR-4727-5pであり、miR-3682-5pがhsa-miR-3682-5pであり、miR-5090がhsa-miR-5090であり、miR-337-3pがhsa-miR-337-3pであり、miR-488-5pがhsa-miR-488-5pであり、miR-100-5pがhsa-miR-100-5pであり、miR-4520-3pがhsa-miR-4520-3pであり、miR-373-3pがhsa-miR-373-3pであり、miR-6499-5pがhsa-miR-6499-5pであり、miR-3909がhsa-miR-3909であり、miR-32-5pがhsa-miR-32-5pであり、miR-302a-3pがhsa-miR-302a-3pであり、miR-4686がhsa-miR-4686であり、miR-4659a-3pがhsa-miR-4659a-3pであり、miR-4287がhsa-miR-4287であり、miR-1301-5pがhsa-miR-1301-5pであり、miR-593-3pがhsa-miR-593-3pであり、miR-517a-3pがhsa-miR-517a-3pであり、miR-517b-3pがhsa-miR-517b-3pであり、miR-142-3pがhsa-miR-142-3pであり、miR-1185-2-3pがhsa-miR-1185-2-3pであり、miR-602がhsa-miR-602であり、miR-527がhsa-miR-527であり、miR-518a-5pがhsa-miR-518a-5pであり、miR-4682がhsa-miR-4682であり、miR-28-5pがhsa-miR-28-5pであり、miR-4252がhsa-miR-4252であり、miR-452-5pがhsa-miR-452-5pであり、miR-525-5pがhsa-miR-525-5p、miR-3622a-3pがhsa-miR-3622a-3p、miR-6813-3pがhsa-miR-6813-3p、miR-4769-3pがhsa-miR-4769-3pであり、miR-371a-5pがhsa-miR-371a-5pであり、miR-6765-3pがhsa-miR-6765-3pであり、miR-6784-5pがhsa-miR-6784-5pであり、miR-6778-5pがhsa-miR-6778-5pであり、miR-6875-5pがhsa-miR-6875-5pであり、miR-4534がhsa-miR-4534であり、miR-4721がhsa-miR-4721であり、miR-6756-5pがhsa-miR-6756-5pであり、miR-615-5pがhsa-miR-615-5pであり、miR-6727-5pがhsa-miR-6727-5pであり、miR-6887-5pがhsa-miR-6887-5pであり、miR-8063がhsa-miR-8063であり、miR-6880-5pがhsa-miR-6880-5pであり、miR-6805-3pがhsa-miR-6805-3pであり、miR-4726-5pがhsa-miR-4726-5pであり、miR-4710がhsa-miR-4710であり、miR-7111-5pがhsa-miR-7111-5pであり、miR-3619-3pがhsa-miR-3619-3pであり、miR-6795-5pがhsa-miR-6795-5pであり、miR-1254がhsa-miR-1254であり、miR-1233-5pがhsa-miR-1233-5pであり、miR-6836-3pがhsa-miR-6836-3pであり、miR-6769a-5pがhsa-miR-6769a-5pであり、miR-4532がhsa-miR-4532であり、miR-365a-5pがhsa-miR-365a-5pであり、miR-1231がhsa-miR-1231であり、miR-1228-5pがhsa-miR-1228-5pであり、miR-4430がhsa-miR-4430であり、miR-296-3pがhsa-miR-296-3pであり、miR-1237-5pがhsa-miR-1237-5pであり、miR-4466がhsa-miR-4466であり、miR-6789-5pがhsa-miR-6789-5pであり、miR-4632-5pがhsa-miR-4632-5pであり、miR-4745-5pがhsa-miR-4745-5pであり、miR-4665-5pがhsa-miR-4665-5pであり、miR-6807-5pがhsa-miR-6807-5pであり、miR-7114-5pがhsa-miR-7114-5pであり、miR-516a-5pがhsa-miR-516a-5pであり、miR-769-3pがhsa-miR-769-3pであり、miR-3692-5pがhsa-miR-3692-5pであり、miR-3945がhsa-miR-3945がであり、miR-4433a-3pがhsa-miR-4433a-3pであり、miR-4485-3pがhsa-miR-4485-3pであり、miR-6831-5pがhsa-miR-6831-5pであり、miR-519c-5pがhsa-miR-519c-5pであり、miR-551b-5pがhsa-miR-551b-5pであり、miR-1343-3pがhsa-miR-1343-3pであり、miR-4286がhsa-miR-4286であり、miR-4634がhsa-miR-4634であり、miR-4733-3pがhsa-miR-4733-3pであり、miR-6086がhsa-miR-6086である。
(a)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択される。
miR-6809-3pがhsa-miR-6809-3pであり、miR-6815-5pがhsa-miR-6815-5pであり、miR-6857-3pがhsa-miR-6857-3pであり、miR-6878-3pがhsa-miR-6878-3pであり、miR-766-3pがhsa-miR-766-3pであり、miR-1229-3pがhsa-miR-1229-3pであり、miR-1306-5pがhsa-miR-1306-5pであり、miR-210-5pがhsa-miR-210-5pであり、miR-198がhsa-miR-198であり、miR-485-3pがhsa-miR-485-3pであり、miR-668-3pがhsa-miR-668-3pであり、miR-532-3pがhsa-miR-532-3pであり、miR-877-3pがhsa-miR-877-3pであり、miR-1238-3pがhsa-miR-1238-3pであり、miR-3130-5pがhsa-miR-3130-5pであり、miR-4298がhsa-miR-4298であり、miR-4290がhsa-miR-4290であり、miR-3943がhsa-miR-3943であり、miR-346がhsa-miR-346であり、miR-767-3pがhsa-miR-767-3pである。
(f)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択される。
(a)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号194~210、374、及び1315~1350のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択される。
一実施形態において本発明の方法における標的核酸は、miR-1225-3p、miR-3184-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p及びmiR-3665からなる群から選択される少なくとも1つのポリヌクレオチドと特異的に結合可能な核酸をさらに含むことができる。
(f)配列番号211~212及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~212及び1351~1356のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~212及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~212及び1351~1356のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択される。
(a)被験体の検体から調製されたRNA(ここで、ステップ(b)の定量RT-PCRのために、例えばRNAの3’末端はポリアデニル化されていてもよい、又はいずれか若しくは両方の末端に任意の配列がライゲーション法などで付加されていてもよい)又はそれから転写された相補的ポリヌクレオチド(cDNA)を、本発明のキットのポリヌクレオチドと結合させるステップ、
(b)当該ポリヌクレオチドに結合した検体由来のRNA又は当該RNAから合成されたcDNAを、上記ポリヌクレオチドを核酸プローブとして用いるハイブリダイゼーションによって、あるいは、上記ポリヌクレオチドをプライマーとして用いる定量RT-PCRによって測定するステップ、
(c)上記(b)の測定結果に基づいて、認知症(又は認知症由来の遺伝子)の存在又は不存在を評価するステップ、
を含むことができる。
(a)認知症患者由来であること及び認知症を罹患していない被験体であることが既に知られている検体中の標的遺伝子の発現量を、本発明による検出用ポリヌクレオチド、キット又はDNAチップを用いて測定するステップ、
(b)(a)で測定された発現量の測定値から、上記の式1~3、5及び6の判別式を作成するステップ、
(c)被験体由来の検体中の当該標的遺伝子の発現量を、本発明による診断(検出)用ポリヌクレオチド、キット又はDNAチップを用いて測定し、(b)で作成した判別式にそれらを代入して、得られた結果に基づいて被験体が認知症を罹患していること又は認知症を罹患していないことを決定又は評価する、或いは認知症患者由来発現量を認知症に罹患していない被験者由来の対照と比較し評価する、ステップ、
を含むことができる。ここで、式1~3、5及び6の式中のxは説明変数であり、上記2節に記載したポリヌクレオチド類から選択されるポリヌクレオチド又はその断片を測定することによって得られる値を含み、具体的には本発明の認知症患者と認知症に罹患していない被験者を判別するための説明変数は、例えば下記より選択される遺伝子発現量である:
配列番号1~210、211~249、250~374、375~390、1315~1350、1351~1356、1435~1448、及び1449~1453のいずれかで表される塩基配列又はその相補的配列において、15以上の連続した塩基を含むDNAのいずれかによって測定される認知症患者及び認知症に罹患していない被験者の血清における遺伝子発現量。
配列番号194~210、374、及び1315~1350並びに211~212及び1351~1356のいずれかで表される塩基配列又はその相補的配列において、15以上の連続した塩基を含むDNAのいずれかによって測定される認知症患者及び認知症に罹患していない被験者の血清における遺伝子発現量。
<検体の採取>
インフォームドコンセントを得た認知症患者(医師の診断により認知症であることが確定している患者)1,496人及び非認知症被験者110人、の合計1,606人からベノジェクトII真空採血管VP-AS109K60(テルモ株式会社(日本))を用いてそれぞれ血清を採取した(表2)。
検体として上記の合計1,606人それぞれから得られた血清300μLから、3D-Gene(登録商標)RNA extraction reagent from liquid sample kit(東レ株式会社(日本))中のRNA抽出用試薬を用いて、同社の定めるプロトコールに従ってtotal RNAを得た。
検体として上記の合計1,606人の血清から得たtotal RNAに対して、3D-Gene(登録商標) miRNA Labeling kit(東レ株式会社)を用いて同社が定めるプロトコールに基づいてmiRNAを蛍光標識した。オリゴDNAチップとして、miRBase release 21に登録されているmiRNAの中で、2,565種のmiRNAと相補的な配列を有するプローブを搭載した3D‐Gene(登録商標) Human miRNA Oligo chip(東レ株式会社)を用い、同社が定めるプロトコールに基づいてストリンジェントな条件下でハイブリダイゼーション及びハイブリダイゼーション後の洗浄を行った。DNAチップを3D-Gene(登録商標)スキャナー(東レ株式会社)を用いてスキャンし、画像を取得して3D-Gene(登録商標)Extraction(東レ株式会社)にて蛍光強度を数値化した。数値化された蛍光強度を、底が2の対数値に変換して遺伝子発現量とし、ブランク値の減算を行い、欠損値はシグナル値0.1で置換した。その結果、上記の1,606人の血清に対する、網羅的なmiRNAの遺伝子発現量を得た。次に、認知症の判別分析に用いる検体を抽出した。まず、陽性検体群を認知症患者とし、陰性検体群を非認知症被検者とした。次に、各検体群を、以下の各実施例で示すように、学習検体群と検証検体群に振り分けた。数値化されたmiRNAの遺伝子発現量を用いた計算及び統計解析は、R言語3.3.1(R Core Team(2016). R: A language and environment for statistical computing. R Foundation for Statistical Computing、Vienna、Austria. URL https://www.R-project.org/.)及びMASSパッケージ7.3.45(Venables、W. N. & Ripley、B. D.(2002) Modern Applied Statistics with S. Fourth Edition. Springer、New York. ISBN 0-387-95457-0)を用いて実施した。
実施例1では、LASSO法を用いたロジスティック回帰による解析を行った。
認知症の一種であるアルツハイマー型認知症の患者と非認知症被検者を判別可能なマーカーを探索する目的で、アルツハイマー型認知症患者及び非認知症被検者の各検体のうち75検体を学習検体群(表3-1のB)に、残りの全検体を検証検体群(表3-1のC)に振り分けた。
認知症の一種である血管性認知症患者と非認知症被検者を判別可能なマーカーを探索する目的で、血管性認知症患者及び非認知症被検者の各検体のうち50検体を学習検体群(表3-1のD)に、残りの全検体を検証検体群(表3-1のE)に振り分けた。
なるべく多くの検体を学習群に振り分け、精度の高いマーカーを探索する目的で、血管性認知症患者及び非認知症被検者の各検体のうち約3分の2の検体を学習検体群(表3-2のF)に、残りの全検体を検証検体群(表3-2のG)に振り分けた。
認知症の一種であるレビー小体型認知症の患者と非認知症被検者を判別可能なマーカーを探索する目的で、レビー小体型認知症患者及び非認知症被検者の各検体のうち75検体を学習検体群(表3-2のH)に、残りの全検体を検証検体群(表3-2のI)に振り分けた。
なるべく多くの検体を学習群に振り分け、精度の高いマーカーを探索する目的で、レビー小体型認知症患者及び非認知症被検者の各検体のうち約3分の2の検体を学習検体群(表3-3のJ)に、残りの全検体を検証検体群(表3-3のK)に振り分けた。
認知症の一種である前頭側頭葉変性症患者と非認知症被検者を判別可能なマーカーを探索する目的で、前頭側頭葉変性症患者及び非認知症被検者の各検体のうち30検体を学習検体群(表3-3のL)に、残りの全検体を検証検体群(表3-3のM)に振り分けた。
認知症の一種である正常圧水頭症患者と非認知症被検者を判別可能なマーカーを探索する目的で、正常圧水頭症患者及び非認知症被検者の各検体のうち30検体を学習検体群(表3-4のN)に、残りの全検体を検証検体群(表3-4のO)に振り分けた。
なるべく多くの検体を学習群に振り分け、精度の高いマーカーを探索する目的で、正常圧水頭症患者及び非認知症被検者の各検体のうち約3分の2の検体を学習検体群(表3-4のP)に、残りの全検体を検証検体群(表3-4のQ)に振り分けた。
実施例2では、実施例1で感度または特異度が80%を超える優れた判別性能を有する複数のマーカーセットが得られたため、実施例1を深化させ、検体群分けを様々に変えることで感度・特異度いずれも70%もしくは80%を超えるマーカーセットが得られるかを検討することを目的とした。
認知症の一種であるアルツハイマー型認知症の患者1,147検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度ともに80%を超える判別式は得られなかったが、70%を超える判別式が3種得られた。
認知症の一種である血管性認知症の患者80検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度80%を超える判別式が8種得られた。
認知症の一種であるレビー小体型認知症の患者159検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度80%を超える判別式が6種得られた。
認知症の一種である前頭側頭葉変性症の患者40検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度ともに80%を超える判別式は得られなかったが、70%を超える判別式が2種得られた。
認知症の一種である前頭側頭葉変性症患者70検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度80%を超える判別式が3種得られた。
実施例3では、以下の二つを目的として行った。
目的1:実施例2の補足として、実施例2と統計手法を変え、実施例2と同様に検体群分けを様々に変えて実施例1を深化させた解析を行うこと
目的2:判別に用いるマーカー数を5つまで減らした場合にも、感度・特異度70%もしくは80%を超えるマーカーセットが得られるか検討を行うこと
認知症の一種であるアルツハイマー型認知症の患者1,147検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度ともに80%を超える判別式は得られなかったが、70%を超える判別式が4種得られた。
認知症の一種である血管性認知症患者80検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度80%を超える判別式が2種得られた。
認知症の一種であるレビー小体型認知症の患者159検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度80%を超える判別式が2種得られた。
認知症の一種である前頭側頭葉変性症の患者40検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度ともに80%を超える判別式は得られなかったが、70%を超える判別式が2種得られた。
認知症の一種である正常圧水頭症の患者70検体、非認知症被検者110検体を用いて解析を行った。その結果、検証群で感度、特異度80%を超える判別式が3種得られた。
実施例4では、実施例3の目的2の検討をさらに深化させ、判別に用いるマーカー数を3個まで減らした場合のバリデーションを検討することを目的とした。具体的には、学習群を用いて、相関の高いマーカーを除外した上でP値上位30種のうち3種を総当たりでフィッシャー判別手法による判別式構築を行い、検証群で性能を評価した。その他は実施例3と同様の手法で行った。
認知症の一種であるアルツハイマー型認知症の患者1,147検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、25種の様々な組み合わせ(第36~第60)とその判別性能を表8に示した。なお、検証群で感度、特異度70%を超える判別式は第55の1種であった(表8)。
認知症の一種である血管性認知症の患者80検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、25種の様々な組み合わせ(第61~第85)とその判別性能を表8に示した。なお、検証群で感度、特異度80%を超える判別式は第80、第81の2種であった(表8)。
認知症の一種であるレビー小体型認知症の患者159検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、25種の様々な組み合わせ(第86~第110)とその判別性能を表8に示した。なお、検証群で感度、特異度80%を超える判別式は第87、第101の2種であった(表8)。
認知症の一種である前頭側頭葉変性症の患者40検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、25種の様々な組み合わせ(第111~第135)とその判別性能を表8に示した。なお、検証群で感度、特異度70%を超える判別式は第133の1種であった(表8)。
認知症の一種である正常圧水頭症の患者70検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、25種の様々な組み合わせ(第136~第160)とその判別性能を表8に示した。なお、検証群で感度、特異度80%を超える判別式は第139、第145、第147、第153、第158の5種であった(表8)。
実施例5では、実施例3、4の検討をさらに深化させ、判別に用いるマーカー数を8個まで増やした場合のバリエーションを検討することを目的とした。具体的には、実施例2と同様に検体を陽性群、陰性群ともそれぞれ5分割し、分割した5分の4を学習群、5分の1を検証群とした。検証群は5回入れ替え、検証群を入れ替えるごとに、学習群を用いて実施例1-1と同様にLASSO法を用いたロジスティック回帰による判別式構築を行い、検証群で性能を評価した。さらに分割方法は5回変更した。
認知症の一種であるレビー小体型認知症の患者159検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、3種の組み合わせ(第161~第163)とその判別性能を表9に示した。3種とも検証群で感度、特異度70%を超える判別式を得ることができた(表9)。
認知症の一種である前頭側頭葉変性症の患者40検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、6種の組み合わせ(第164~第169)とその判別性能を表9に示した。検証群で感度、特異度70%を超える判別式は第165、第166、第167の3種得られた(表9)。
認知症の一種である正常圧水頭症の患者70検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、3種の組み合わせ(第170~第172)とその判別性能を表9に示した。検証群で感度、特異度70%を超える判別式は第171の1種得られた(表9)。
実施例6では、実施例3~5の検討をさらに深化させ、判別に用いるマーカー数を9個まで増やした場合のバリエーションを検討することを目的とした。具体的には、実施例5と同様に行った。
認知症の一種であるアルツハイマー型認知症の患者1,147検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、6種の組み合わせ(第173~第178)とその判別性能を表10に示した。第173、第175、第176、第177、第178の5種では検証群で感度、特異度のいずれかが70%を超えるマーカーセットのバリエーションを見出すことができた(表10)。
認知症の一種である血管性認知症の患者80検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、4種の組み合わせ(第179~第182)とその判別性能を表10に示した。第179、第181の2種は検証群で感度、特異度のいずれかが80%を超えるマーカーセットのバリエーションを見出すことができた(表10)。
認知症の一種であるレビー小体型認知症の患者159検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、8種の組み合わせ(第183~第190)とその判別性能を表10に示した。このうち第187、第190の2種は検証群で感度、特異度80%を超えるマーカーセットのバリエーションを見出すことができた(表10)。
認知症の一種である前頭側頭葉変性症の患者40検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、3種の組み合わせ(第191~第193)とその判別性能を表10に示した。3種とも感度、特異度のいずれかは70%を超えるマーカーセットのバリエーションを見出すことができた(表10)。
認知症の一種である正常圧水頭症の患者70検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、8種の組み合わせ(第194~第201)とその判別性能を表10に示した。このうち第194、第195、第198の3種は検証群で感度、特異度80%を超えるマーカーセットのバリエーションを見出すことができた(表10)。
実施例7では、実施例3~6の検討をさらに深化させ、判別に用いるマーカー数を10個まで増やした場合のバリデーションを検討することを目的とした。具体的には、実施例5と同様に行った。
認知症の一種であるアルツハイマー型認知症の患者1,147検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、17種の組み合わせ(第202~第218)とその判別性能を表11に示した。このうち第204、第206、第209の3種では検証群で感度、特異度70%を超えるマーカーセットのバリエーションを見出すことができた(表11)。
認知症の一種である血管性認知症の患者80検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、21種の組み合わせ(第219~第239)とその判別性能を表11に示した。このうち第219、第222、第225、第226、第232、第234、第235、第236、第239の9種では検証群で感度、特異度80%を超えるマーカーセットのバリエーションを見出すことができた(表11)。
認知症の一種であるレビー小体型認知症の患者159検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、14種の組み合わせ(第240~第253)とその判別性能を表11に示した。
認知症の一種である前頭側頭葉変性症の患者40検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、16種の組み合わせ(第254~第269)とその判別性能を表11に示した。このうち第269の1種では検証群で感度、特異度70%を超えるマーカーセットのバリエーションを見出すことができた(表11)。
認知症の一種である正常圧水頭症の患者70検体、非認知症被検者110検体を用いて解析を行った。その結果得られた、14種の組み合わせ(第270~第283)とその判別性能を表11に示した(表11)。
実施例8では、アルツハイマー型認知症について、実施例3のP値上位30種と増やすことで、実施例3よりも感度・特異度が向上するか検討を行うことを目的とした。
認知症の一種であるアルツハイマー型認知症の患者1,147検体、非認知症被検者110検体を用いて解析を行った。P値上位30種のうち4種を用いた。その結果、検証群で感度、特異度ともに70%を超える判別式が3種(第284~第286)得られ、その組み合わせとその判別性能を表12に示した。
認知症の一種であるアルツハイマー型認知症の患者1,147検体、非認知症被検者110検体を用いて解析を行った。P値上位30種のうち5種を用いた。その結果、検証群で感度、特異度ともに70%を超える判別式が3種(第287~第289)得られ、その組み合わせとその判別性能を表12に示した。
実施例9では、実施例1~8と統計手法を変えた解析を行い、判別精度の高いマーカーセットを構築することを目的とした。具体的には、まず上記の参考例1で得たmiRNA発現量を合わせてglobal normalizationで正規化した。次に単変量のロジスティック回帰で各miRNAの検定統計量(z値)を算出し、z値があるカットオフT値より大きいmiRNAを選出した。この選出したmiRNAのみを用いて主成分分析を行い、主成分得点を算出した。この上位の主成分得点を説明変数にした多重ロジスティック回帰式を作成した。この操作をT値と主成分得点とを変えて全検索し、10回交差検証を行いT値と主成分得点を最適化した。この最適化したT値と主成分得点を用いて予測式を選定し、この予測式を独立した別検体で検証した。
実施例9―1では参考例1で記載した認知症の一種であるアルツハイマー型認知症の患者のうち1,021検体と、参考例1で記載した非認知症被験者に参考例1と同様にして採取した認知症以外のその他疾患を含む被験者を合わせた非認知症被検者288検体を用いて解析を行った。このうちアルツハイマー型認知症患者511検体、非認知症被検者144検体を学習群とし、残りの全検体、すなわちアルツハイマー型認知症患者510検体、非認知症被検者144検体を検証群とした。判別マーカーとして配列番号8、15、34、40、133、191、212、250~316及び375~378で示される78個のmiRNAを用い、T値を4.5、10個の主成分得点を用いた場合、検証群でアルツハイマー型認知症をAUC値=0.874という値で予測可能であった。このとき予測指標値のカットオフを0.281とすると、精度87%、感度93%、特異度66%であった(表13)。
実施例9―2では、参考例1で記載した血管性認知症患者に参考例1と同様にして採取した血管性認知症患者を合わせた91検体と、実施例9-1と同様の非認知症被検者288検体を用いて解析を行った。このうち血管性認知症患者46検体、非認知症被検者144検体を学習群とし、残りの全検体、すなわち血管性認知症患者45検体、非認知症被検者144検体を検証群とした。判別マーカーとして配列番号3、8、15、26、34、69、99、101、109、112、125、133、191~194、252、255、258、261~264、266、267、271、277、278、282、284、287、289、290、293、294、297、298、301、303、306、307、310、312~314、320、321、323、327、329、335、336、338、342、343、345、348、349、351、352、354、359、361~373及び375、376、380~383、385、387~390で示される86個のmiRNAを用い、T値を4.0、10個の主成分得点を用いた場合、検証群で血管性認知症をAUC値=0.867という値で予測可能であった。このとき予測指標値のカットオフを0.761とすると、精度84%、感度73%、特異度87%であった(表13)。
実施例9―3では、参考例1で記載したレビー小体型認知症患者に参考例1と同様にして採取したレビー小体型認知症患者を合わせた169検体、実施例9-1と同様の非認知症被検者288検体を用いて解析を行った。このうちレビー小体型認知症患者85検体、非認知症被検者144検体を学習群とし、残りの全検体、すなわちレビー小体型認知症患者84検体、非認知症被検者144検体を検証群とした。判別マーカーとして配列番号3、8、15、26、34、53、99、101、107、109、112、128、133、191、192、194、250、253~258、261、262、264~267、271、277、279、282~284、287、289、290、293、294、298、299、301~303、306、308、310、312~314、316~360、374~377、379~388で示される110個のmiRNAを用い、T値を3.4、9個の主成分得点を用いた場合、検証群でレビー小体型認知症をAUC値=0.870という値で予測可能であった。このとき予測指標値のカットオフを0.0392とすると、精度83%、感度76%、特異度86%であった(表13)。
実施例9-1で作成した判別式を用いて、認知症発症前段階である軽度認知機能障害者32検体が認知症に進行するか否かの進行予測を行った。このうち10検体が少なくとも6か月後に臨床判断でアルツハイマー型認知症に進行した。予測指標値のカットオフを0.281とすると、この進行した10検体すべてを感度100%で予測可能であった。また、アルツハイマー型認知症に進行しなかった4検体すべてを特異度100%で予測可能であった。一方、これ以外の残る18検体の判別結果はアルツハイマー型認知症に進行すると予測したが、臨床判断では軽度認知機能障害であり、引き続き経過観察中である。
<検体の採取>
インフォームドコンセントを得た認知症患者(医師の診断により認知症であることが確定している患者)1,972人及び非認知症被験者1,006人、の合計2,978人からベノジェクトII真空採血管VP-AS109K60(テルモ株式会社(日本))を用いてそれぞれ血清を採取した。認知症患者の病型の内訳は、1:アルツハイマー型認知症患者1,147人、2:アルツハイマー型認知症と血管性認知症との併発患者151人、3:アルツハイマー型認知症の疑い及びアルツハイマー型認知症と血管性認知症以外の認知症との併発患者240人、4:血管性認知症患者80人、5:「その他の認知症」(アルコール性認知症、ビタミン欠乏性認知症などの他の疾患を病因とする認知症及び病型不明又は特定不能の認知症。以下の実施例において同じ。)患者85人、6:レビー小体型認知症患者159人、7:前頭側頭葉変性症患者40人、8:正常圧水頭症患者70人であった。また、非認知症被検者の内訳は、9:認知症以外の疾患を罹患していない被検者110人、10:認知症以外の疾患を罹患している被検者896人であった(表14)。
検体として上記の合計2,978人それぞれから得られた血清300μLから、3D-Gene(登録商標)RNA extraction reagent from liquid sample kit(東レ株式会社(日本))中のRNA抽出用試薬を用いて、同社の定めるプロトコールに従ってtotal RNAを得た。
検体として上記の合計2,978人の血清から得たtotal RNAに対して、3D-Gene(登録商標)miRNA Labeling kit(東レ株式会社)を用いて同社が定めるプロトコールに基づいてmiRNAを蛍光標識した。オリゴDNAチップとして、miRBase release 21に登録されているmiRNAの中で、2,565種のmiRNAと相補的な配列を有するプローブを搭載した3D-Gene(登録商標)Human miRNA Oligo chip(東レ株式会社)を用い、同社が定めるプロトコールに基づいてストリンジェントな条件下でハイブリダイゼーション及びハイブリダイゼーション後の洗浄を行った。DNAチップを3D-Gene(登録商標)スキャナー(東レ株式会社)を用いてスキャンし、画像を取得して3D-Gene(登録商標)Extraction(東レ株式会社)にて蛍光強度を数値化した。数値化された蛍光強度を、底が2の対数値に変換して遺伝子発現量とし、ブランク値の減算を行い、欠損値はシグナル値0.1で置換した。その結果、上記の2,978人の血清に対する、網羅的なmiRNAの遺伝子発現量を得た。
本実施例では、認知症患者、非認知症被検者のどちらもバランスよく判別可能なマーカーを探索する目的で、認知症患者及び非認知症被検者の各検体のうち900検体を学習検体群(表15のB)に、残りの全検体を検証検体群(表15のC)に振り分けた。すなわち、表15に示すように、認知症患者の全検体のうち900検体(1:アルツハイマー型認知症患者522人、2:アルツハイマー型認知症と血管性認知症との併発患者73人、3:アルツハイマー型認知症の疑い及びアルツハイマー型認知症と血管性認知症以外の認知症との併発患者99人、4:血管性認知症患者34人、5:「その他の認知症」患者46人、6:レビー小体型認知症患者72人、7:前頭側頭葉変性症患者20人、8:正常圧水頭症患者34人)及び非認知症被検者の全検体のうち900人(9:認知症以外の疾患を罹患していない被検者102人、10:認知症以外の疾患を罹患している被検者798人)を学習検体群とし、認知症患者の全検体のうち1072検体(1:アルツハイマー型認知症患者625人、2:アルツハイマー型認知症と血管性認知症の併発患者78人、3:アルツハイマー型認知症の疑い及びアルツハイマー型認知症と血管性認知症以外の認知症の併発患者141人、4:血管性認知症患者46人、5:「その他の認知症」患者39人、6:レビー小体型認知症患者87人、7:前頭側頭葉変性症患者20人、8:正常圧水頭症患者36人)及び非認知症被検者の全検体のうち106検体(9:認知症以外の疾患を罹患していない被検者8人、10:認知症以外の疾患を罹患している被検者98人)を検証検体群とした。
その結果、判別マーカーとして配列番号1315~1316、194で示される3個のmiRNAを用いた場合、検証検体群における感度70%、特異度56%である判別式が得られた(表17)。
実施例11と同様にして、認知症に罹患しているか否かを判別する判別式を、11個のmiRNAの組合せを用いて構築し、検証した。
実施例1と同様にして、認知症に罹患しているか否かを判別する判別式を、20個のmiRNAの組合せを用いて構築し、検証した。
その結果、判別マーカーとして配列番号1315、1316、194、195、1318、1319、197、1320~1325、199、1331、200、1335、1352、1354、1356で示される20個のmiRNAを用いた場合、検証検体群における感度70%、特異度64%である判別式が得られた(表17)。miRNAマーカーを11個から20個に増やすことで、さらなる特異度向上(偽陽性低下)が確認できた。
実施例11と同様にして、認知症に罹患しているか否かを判別する判別式を26個のmiRNAの組合せを用いて構築し、検証した。
実施例11と同様にして、認知症に罹患しているか否かを判別する判別式を42個のmiRNAの組合せを用いて構築し、検証した。
本実施例では、特に認知症患者を感度よく判別可能なマーカーを探索する目的で、各検体群の約3分の2の検体を学習検体群(表16のB)に、残りの全検体を検証検体群(表16のC)に振り分けた。すなわち、表16に示すように、認知症患者の全検体のうち1,315検体(1:アルツハイマー型認知症患者774人、2:アルツハイマー型認知症と血管性認知症との併発患者108人、3:アルツハイマー型認知症の疑い及びアルツハイマー型認知症と血管性認知症以外の認知症との併発患者150人、4:血管性認知症患者48人、5:「その他の認知症」患者58人、6:レビー小体型認知症患者106人、7:前頭側頭葉変性症患者27人、8:正常圧水頭症患者44人)及び非認知症被検者の全検体のうち671検体(9:認知症以外の疾患を罹患していない被検者71人、10:認知症以外の疾患を罹患している被検者600人)を学習検体群とし、認知症患者の全検体のうち657検体(1:アルツハイマー型認知症患者373人、2:アルツハイマー型認知症と血管性認知症との併発患者43人、3:アルツハイマー型認知症の疑い及びアルツハイマー型認知症と血管性認知症以外の認知症との併発患者90人、4:血管性認知症患者32人、5:「その他の認知症」患者27人、6:レビー小体型認知症患者53人、7:前頭側頭葉変性症患者13人、8:正常圧水頭症患者26人)及び非認知症335検体(9:認知症以外の疾患を罹患していない被検者39人、10:認知症以外の疾患を罹患している被検者296人)を検証検体群とした。
実施例16と同様にして、認知症に罹患しているか否かを判別する判別式を、10個のmiRNAの組合せを用いて構築し、検証した。
実施例16と同様にして、認知症に罹患しているか否かを判別する判別式を、20個のmiRNAの組合せを用いて構築し、検証した。
実施例16と同様にして、認知症に罹患しているか否かを判別する判別式を、39個のmiRNAの組合せを用いて構築し、検証した。
実施例16と同様にして、認知症に罹患しているか否かを判別する判別式を、51個のmiRNAの組合せを用いて構築し、検証した。
認知症を早期に検出し早期に治療を行うためには、取り漏らしなく診断することが求められる。一方で、認知症は診断されると社会的インパクトが大きな疾患であるため、偽陽性なく精度よく診断できることもまた重要である。上記の実施例11~20より、配列番号1~54、55~62及び127~178で表される塩基配列からなる全てのポリヌクレオチドは、1個、2個もしくはそれ以上の個数の組合せ、好ましくは20個~60個、より好ましくは40個~55個で、認知症患者と認知症に罹患していない被験者を高精度で判別できる遺伝子だと言える。
実施例11と同様にして、認知症に罹患しているか否かを判別する判別式を、2個のmiRNAの組合せを用いて構築し、検証した。
実施例11と同様にして、認知症に罹患しているか否かを判別する判別式を、1個のmiRNAを用いて構築し、検証した。
実施例24では、認知症判別により適した統計手法を探索する目的で、実施例11~23で用いた統計手法LASSO法、Elastic net、及びRidge回帰を比較した。この検討には、参考例2で記載した認知症患者、被認知症被験者に参考例2と同様にして採取した認知症患者、被認知症被験者を合わせた、認知症患者2,177検体と非認知症被検者756検体を用いて解析を行った。具体的には、まず上記の参考例2で得たmiRNA発現量を合わせてglobal normalizationで正規化した。次に検体の分割を行い、全検体の4分の3を学習検体群、残る4分の1を検証検体群とした。さらに学習検体群を5分割し、LASSO法、Elastic net、Ridge回帰、それぞれを用いた多重ロジスティック回帰でmiRNAごとのp値を算出し、p値上位から順に変数を増やして、5分割の交差検証により最適なmiRNA数を検討した。
本明細書で引用した全ての刊行物、特許及び特許出願はそのまま引用により本明細書に組み入れられるものとする。
Claims (36)
- 認知症マーカーである、miR-4274、miR-4272、miR-4728-5p、miR-4443、miR-4506、miR-6773-5p、miR-4662a-5p、miR-3184-3p、miR-4281、miR-320d、miR-6729-3p、miR-5192、miR-6853-5p、miR-1234-3p、miR-1233-3p、miR-4539、miR-3914、miR-4738-5p、miR-548au-3p、miR-1539、miR-4720-3p、miR-365b-5p、miR-4486、miR-1227-5p、miR-4667-5p、miR-6088、miR-6820-5p、miR-4505、miR-548q、miR-4658、miR-450a-5p、miR-1260b、miR-3677-5p、miR-6777-3p、miR-6826-3p、miR-6832-3p、miR-4725-3p、miR-7161-3p、miR-2277-5p、miR-7110-3p、miR-4312、miR-4461、miR-6766-5p、miR-1266-3p、miR-6729-5p、miR-526b-3p、miR-519e-5p、miR-512-5p、miR-5088-5p、miR-1909-3p、miR-6511a-5p、miR-4734、miR-936、miR-1249-3p、miR-6777-5p、miR-4487、miR-3155a、miR-563、miR-4741、miR-6788-5p、miR-4433b-5p、miR-323a-5p、miR-6811-5p、miR-6721-5p、miR-5004-5p、miR-6509-3p、miR-648、miR-3917、miR-6087、miR-1470、miR-586、miR-3150a-5p、miR-105-3p、miR-7973、miR-1914-5p、miR-4749-3p、miR-15b-5p、miR-1289、miR-4433a-5p、miR-3666、miR-3186-3p、miR-4725-5p、miR-4488、miR-4474-3p、miR-6731-3p、miR-4640-3p、miR-202-5p、miR-6816-5p、miR-638、miR-6821-5p、miR-1247-3p、miR-6765-5p、miR-6800-5p、miR-3928-3p、miR-3940-5p、miR-3960、miR-6775-5p、miR-3178、miR-1202、miR-6790-5p、miR-4731-3p、miR-2681-3p、miR-6758-5p、miR-8072、miR-518d-3p、miR-3606-3p、miR-4800-5p、miR-1292-3p、miR-6784-3p、miR-4450、miR-6132、miR-4716-5p、miR-6860、miR-1268b、miR-378d、miR-4701-5p、miR-4329、miR-185-3p、miR-552-3p、miR-1273g-5p、miR-6769b-3p、miR-520a-3p、miR-4524b-5p、miR-4291、miR-6734-3p、miR-143-5p、miR-939-3p、miR-6889-3p、miR-6842-3p、miR-4511、miR-4318、miR-4653-5p、miR-6867-3p、miR-133b、miR-3196、miR-193b-3p、miR-3162-3p、miR-6819-3p、miR-1908-3p、miR-6786-5p、miR-3648、miR-4513、miR-3652、miR-4640-5p、miR-6871-5p、miR-7845-5p、miR-3138、miR-6884-5p、miR-4653-3p、miR-636、miR-4652-3p、miR-6823-5p、miR-4502、miR-7113-5p、miR-8087、miR-7154-3p、miR-5189-5p、miR-1253、miR-518c-5p、miR-7151-5p、miR-3614-3p、miR-4727-5p、miR-3682-5p、miR-5090、miR-337-3p、miR-488-5p、miR-100-5p、miR-4520-3p、miR-373-3p、miR-6499-5p、miR-3909、miR-32-5p、miR-302a-3p、miR-4686、miR-4659a-3p、miR-4287、miR-1301-5p、miR-593-3p、miR-517a-3p、miR-517b-3p、miR-142-3p、miR-1185-2-3p、miR-602、miR-527、miR-518a-5p、miR-4682、miR-28-5p、miR-4252、miR-452-5p、miR-525-5p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、miR-7114-5p、miR-516a-5p、miR-769-3p、miR-3692-5p、miR-3945、miR-4433a-3p、miR-4485-3p、miR-6831-5p、miR-519c-5p、miR-551b-5p、miR-1343-3p、miR-4286、miR-4634、miR-4733-3p、及びmiR-6086からなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を含む、認知症の検出用キット。
- 前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項1に記載のキット。 - 前記キットが、別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、miR-3665、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p、及びmiR-486-5pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、請求項1又は2に記載のキット。
- 前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項3に記載のキット。 - 前記キットが、別の認知症マーカーである、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、及びmiR-6878-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、請求項1~4のいずれか1項に記載のキット。
- 前記核酸が、下記の(k)~(o)のいずれかに示すポリヌクレオチド:
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項5に記載のキット。 - 前記キットが、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、請求項1~6のいずれか1項に記載のキット。
- 前記核酸が、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項7に記載のキット。 - 認知症マーカーである、miR-4728-5p、miR-3184-3p、miR-1233-3p、miR-6088、miR-6777-3p、miR-7110-3p、miR-936、miR-6087、miR-1202、miR-4731-3p、miR-4800-5p、miR-6784-3p、miR-4716-5p、miR-6734-3p、miR-6889-3p、miR-6867-3p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-3184-5p、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、miR-6878-3p、及びmiR-371a-5pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸Iを含み、
任意に、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸IIをさらに含む、認知症の検出又は予測用キット。 - 前記核酸Iが、下記の(u)~(y)のいずれかに示すポリヌクレオチド:
(u)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(v)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列を含むポリヌクレオチド、(w)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(x)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(y)前記(u)~(x)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドであり、
前記核酸IIが、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項9に記載のキット。 - 認知症マーカーである、miR-4274、miR-4272、miR-4728-5p、miR-4443、miR-4506、miR-6773-5p、miR-4662a-5p、miR-3184-3p、miR-4281、miR-320d、miR-6729-3p、miR-5192、miR-6853-5p、miR-1234-3p、miR-1233-3p、miR-4539、miR-3914、miR-4738-5p、miR-548au-3p、miR-1539、miR-4720-3p、miR-365b-5p、miR-4486、miR-1227-5p、miR-4667-5p、miR-6088、miR-6820-5p、miR-4505、miR-548q、miR-4658、miR-450a-5p、miR-1260b、miR-3677-5p、miR-6777-3p、miR-6826-3p、miR-6832-3p、miR-4725-3p、miR-7161-3p、miR-2277-5p、miR-7110-3p、miR-4312、miR-4461、miR-6766-5p、miR-1266-3p、miR-6729-5p、miR-526b-3p、miR-519e-5p、miR-512-5p、miR-5088-5p、miR-1909-3p、miR-6511a-5p、miR-4734、miR-936、miR-1249-3p、miR-6777-5p、miR-4487、miR-3155a、miR-563、miR-4741、miR-6788-5p、miR-4433b-5p、miR-323a-5p、miR-6811-5p、miR-6721-5p、miR-5004-5p、miR-6509-3p、miR-648、miR-3917、miR-6087、miR-1470、miR-586、miR-3150a-5p、miR-105-3p、miR-7973、miR-1914-5p、miR-4749-3p、miR-15b-5p、miR-1289、miR-4433a-5p、miR-3666、miR-3186-3p、miR-4725-5p、miR-4488、miR-4474-3p、miR-6731-3p、miR-4640-3p、miR-202-5p、miR-6816-5p、miR-638、miR-6821-5p、miR-1247-3p、miR-6765-5p、miR-6800-5p、miR-3928-3p、miR-3940-5p、miR-3960、miR-6775-5p、miR-3178、miR-1202、miR-6790-5p、miR-4731-3p、miR-2681-3p、miR-6758-5p、miR-8072、miR-518d-3p、miR-3606-3p、miR-4800-5p、miR-1292-3p、miR-6784-3p、miR-4450、miR-6132、miR-4716-5p、miR-6860、miR-1268b、miR-378d、miR-4701-5p、miR-4329、miR-185-3p、miR-552-3p、miR-1273g-5p、miR-6769b-3p、miR-520a-3p、miR-4524b-5p、miR-4291、miR-6734-3p、miR-143-5p、miR-939-3p、miR-6889-3p、miR-6842-3p、miR-4511、miR-4318、miR-4653-5p、miR-6867-3p、miR-133b、miR-3196、miR-193b-3p、miR-3162-3p、miR-6819-3p、miR-1908-3p、miR-6786-5p、miR-3648、miR-4513、miR-3652、miR-4640-5p、miR-6871-5p、miR-7845-5p、miR-3138、miR-6884-5p、miR-4653-3p、miR-636、miR-4652-3p、miR-6823-5p、miR-4502、miR-7113-5p、miR-8087、miR-7154-3p、miR-5189-5p、miR-1253、miR-518c-5p、miR-7151-5p、miR-3614-3p、miR-4727-5p、miR-3682-5p、miR-5090、miR-337-3p、miR-488-5p、miR-100-5p、miR-4520-3p、miR-373-3p、miR-6499-5p、miR-3909、miR-32-5p、miR-302a-3p、miR-4686、miR-4659a-3p、miR-4287、miR-1301-5p、miR-593-3p、miR-517a-3p、miR-517b-3p、miR-142-3p、miR-1185-2-3p、miR-602、miR-527、miR-518a-5p、miR-4682、miR-28-5p、miR-4252、miR-452-5p、miR-525-5p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、miR-7114-5p、miR-516a-5p、miR-769-3p、miR-3692-5p、miR-3945、miR-4433a-3p、miR-4485-3p、miR-6831-5p、miR-519c-5p、miR-551b-5p、miR-1343-3p、miR-4286、miR-4634、miR-4733-3p、及びmiR-6086からなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を含む、認知症の検出用デバイス。
- 前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項11に記載のデバイス。 - 前記デバイスが、別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、miR-3665、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p、及びmiR-486-5pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、請求項11又は12に記載のデバイス。
- 前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249、1351~1356及び1449~1453のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項13に記載のデバイス。 - 前記デバイスが、別の認知症マーカーである、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、及びmiR-6878-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、請求項11~14のいずれか1項に記載のデバイス。
- 前記核酸が、下記の(k)~(o)のいずれかに示すポリヌクレオチド:
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項15に記載のデバイス。 - 前記デバイスが、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸をさらに含む、請求項11~16のいずれか1項に記載のデバイス。
- 前記核酸が、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項17に記載のデバイス。 - 認知症マーカーである、miR-4728-5p、miR-3184-3p、miR-1233-3p、miR-6088、miR-6777-3p、miR-7110-3p、miR-936、miR-6087、miR-1202、miR-4731-3p、miR-4800-5p、miR-6784-3p、miR-4716-5p、miR-6734-3p、miR-6889-3p、miR-6867-3p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-3184-5p、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、miR-6878-3p、及びmiR-371a-5pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸Iを含み、
任意に、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチド、又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸IIをさらに含む、認知症の検出又は予測用デバイス。 - 前記核酸Iが、下記の(u)~(y)のいずれかに示すポリヌクレオチド:
(u)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(v)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列を含むポリヌクレオチド、(w)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(x)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(y)前記(u)~(x)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドであり、
前記核酸IIが、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項19に記載のデバイス。 - 前記デバイスが、ハイブリダイゼーション技術による測定のためのデバイスである、請求項11~20のいずれか1項に記載のデバイス。
- 前記ハイブリダイゼーション技術が、核酸アレイ技術である、請求項21に記載のデバイス。
- 被験体の検体において、認知症マーカーである、miR-4274、miR-4272、miR-4728-5p、miR-4443、miR-4506、miR-6773-5p、miR-4662a-5p、miR-3184-3p、miR-4281、miR-320d、miR-6729-3p、miR-5192、miR-6853-5p、miR-1234-3p、miR-1233-3p、miR-4539、miR-3914、miR-4738-5p、miR-548au-3p、miR-1539、miR-4720-3p、miR-365b-5p、miR-4486、miR-1227-5p、miR-4667-5p、miR-6088、miR-6820-5p、miR-4505、miR-548q、miR-4658、miR-450a-5p、miR-1260b、miR-3677-5p、miR-6777-3p、miR-6826-3p、miR-6832-3p、miR-4725-3p、miR-7161-3p、miR-2277-5p、miR-7110-3p、miR-4312、miR-4461、miR-6766-5p、miR-1266-3p、miR-6729-5p、miR-526b-3p、miR-519e-5p、miR-512-5p、miR-5088-5p、miR-1909-3p、miR-6511a-5p、miR-4734、miR-936、miR-1249-3p、miR-6777-5p、miR-4487、miR-3155a、miR-563、miR-4741、miR-6788-5p、miR-4433b-5p、miR-323a-5p、miR-6811-5p、miR-6721-5p、miR-5004-5p、miR-6509-3p、miR-648、miR-3917、miR-6087、miR-1470、miR-586、miR-3150a-5p、miR-105-3p、miR-7973、miR-1914-5p、miR-4749-3p、miR-15b-5p、miR-1289、miR-4433a-5p、miR-3666、miR-3186-3p、miR-4725-5p、miR-4488、miR-4474-3p、miR-6731-3p、miR-4640-3p、miR-202-5p、miR-6816-5p、miR-638、miR-6821-5p、miR-1247-3p、miR-6765-5p、miR-6800-5p、miR-3928-3p、miR-3940-5p、miR-3960、miR-6775-5p、miR-3178、miR-1202、miR-6790-5p、miR-4731-3p、miR-2681-3p、miR-6758-5p、miR-8072、miR-518d-3p、miR-3606-3p、miR-4800-5p、miR-1292-3p、miR-6784-3p、miR-4450、miR-6132、miR-4716-5p、miR-6860、miR-1268b、miR-378d、miR-4701-5p、miR-4329、miR-185-3p、miR-552-3p、miR-1273g-5p、miR-6769b-3p、miR-520a-3p、miR-4524b-5p、miR-4291、miR-6734-3p、miR-143-5p、miR-939-3p、miR-6889-3p、miR-6842-3p、miR-4511、miR-4318、miR-4653-5p、miR-6867-3p、miR-133b、miR-3196、miR-193b-3p、miR-3162-3p、miR-6819-3p、miR-1908-3p、miR-6786-5p、miR-3648、miR-4513、miR-3652、miR-4640-5p、miR-6871-5p、miR-7845-5p、miR-3138、miR-6884-5p、miR-4653-3p、miR-636、miR-4652-3p、miR-6823-5p、miR-4502、miR-7113-5p、miR-8087、miR-7154-3p、miR-5189-5p、miR-1253、miR-518c-5p、miR-7151-5p、miR-3614-3p、miR-4727-5p、miR-3682-5p、miR-5090、miR-337-3p、miR-488-5p、miR-100-5p、miR-4520-3p、miR-373-3p、miR-6499-5p、miR-3909、miR-32-5p、miR-302a-3p、miR-4686、miR-4659a-3p、miR-4287、miR-1301-5p、miR-593-3p、miR-517a-3p、miR-517b-3p、miR-142-3p、miR-1185-2-3p、miR-602、miR-527、miR-518a-5p、miR-4682、miR-28-5p、miR-4252、miR-452-5p、miR-525-5p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-1915-3p、miR-1343-5p、miR-6861-5p、miR-6781-5p、miR-4508、miR-6743-5p、miR-6726-5p、miR-4525、miR-4651、miR-6813-5p、miR-5787、miR-1290、miR-6075、miR-4758-5p、miR-4690-5p、miR-762、miR-371a-5p、miR-6765-3p、miR-6784-5p、miR-6778-5p、miR-6875-5p、miR-4534、miR-4721、miR-6756-5p、miR-615-5p、miR-6727-5p、miR-6887-5p、miR-8063、miR-6880-5p、miR-6805-3p、miR-4726-5p、miR-4710、miR-7111-5p、miR-3619-3p、miR-6795-5p、miR-1254、miR-1233-5p、miR-6836-3p、miR-6769a-5p、miR-4532、miR-365a-5p、miR-1231、miR-1228-5p、miR-4430、miR-296-3p、miR-1237-5p、miR-4466、miR-6789-5p、miR-4632-5p、miR-4745-5p、miR-4665-5p、miR-6807-5p、miR-7114-5p、miR-516a-5p、miR-769-3p、miR-3692-5p、miR-3945、miR-4433a-3p、miR-4485-3p、miR-6831-5p、miR-519c-5p、miR-551b-5p、miR-1343-3p、miR-4286、miR-4634、miR-4733-3p、及びmiR-6086からなる群から選択される1以上のポリヌクレオチドの発現量を測定し、該測定された発現量を用いて、被験体が認知症に罹患しているか否かをin vitroで評価することを含む、認知症の検出方法。
- 認知症であることが既知である被験体由来の検体の遺伝子発現量と非認知症被験体由来の検体の遺伝子発現量を教師サンプルとして作成された、かつ認知症又は非認知症を区別的に判別することが可能である判別式に、上記被験体由来の検体中の前記1以上のポリヌクレオチドの発現量を代入し、それによって、認知症又は非認知症を評価することを含む、請求項23に記載の方法。
- 前記ポリヌクレオチド又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドの発現量の測定を行い、前記核酸が、下記の(a)~(e)のいずれかに示すポリヌクレオチド:
(a)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(b)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列を含むポリヌクレオチド、
(c)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(d)配列番号1~210、374、1315~1350、及び1435~1448のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列を含むポリヌクレオチド、及び
(e)前記(a)~(d)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項23又は24に記載の方法。 - 別の認知症マーカーである、miR-1225-3p、miR-3184-5p、miR-665、miR-211-5p、miR-1247-5p、miR-3656、miR-149-5p、miR-744-5p、miR-345-5p、miR-150-5p、miR-191-3p、miR-651-5p、miR-34a-5p、miR-409-5p、miR-369-5p、miR-1915-5p、miR-204-5p、miR-137、miR-382-5p、miR-517-5p、miR-532-5p、miR-22-5p、miR-1237-3p、miR-1224-3p、miR-625-3p、miR-328-3p、miR-122-5p、miR-202-3p、miR-4781-5p、miR-718、miR-342-3p、miR-26b-3p、miR-140-3p、miR-200a-3p、miR-378a-3p、miR-484、miR-296-5p、miR-205-5p、miR-431-5p、miR-150-3p、miR-423-5p、miR-575、miR-671-5p、miR-939-5p、miR-3665、miR-30d-5p、miR-30b-3p、miR-92a-3p、miR-371b-5p、及びmiR-486-5pからなる群から選択される1以上のポリヌクレオチドの発現量を測定することをさらに含む、請求項23~25のいずれか1項に記載の方法。
- 前記ポリヌクレオチド又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドの発現量の測定を行い、前記核酸が、下記の(f)~(j)のいずれかに示すポリヌクレオチド:
(f)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(g)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列を含むポリヌクレオチド、
(h)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(i)配列番号211~249、1351~1356、及び1449~1453のいずれかで表される塩基配列、もしくは当該塩基配列においてuがtである塩基配列、に相補的な塩基配列を含むポリヌクレオチド、及び
(j)前記(f)~(i)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項26に記載の方法。 - 別の認知症マーカーである、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、及びmiR-6878-3pからなる群から選択される1以上のポリヌクレオチドの発現量を測定することをさらに含む、請求項23~27のいずれか1項に記載の方法。
- 前記ポリヌクレオチド又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドの発現量の測定を行い、前記核酸が、下記の(k)~(o)のいずれかに示すポリヌクレオチド:
(k)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(l)配列番号250~373のいずれかで表される塩基配列を含むポリヌクレオチド、(m)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(n)配列番号250~373のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(o)前記(k)~(n)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項28に記載の方法。 - 別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、miR-767-3pからなる群から選択される1以上のポリヌクレオチドの発現量を測定することをさらに含む、請求項23~29のいずれか1項に記載の方法。
- 前記ポリヌクレオチド又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドの発現量の測定を行い、前記核酸が、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項30に記載の方法。 - 認知症マーカーである、miR-4728-5p、miR-3184-3p、miR-1233-3p、miR-6088、miR-6777-3p、miR-7110-3p、miR-936、miR-6087、miR-1202、miR-4731-3p、miR-4800-5p、miR-6784-3p、miR-4716-5p、miR-6734-3p、miR-6889-3p、miR-6867-3p、miR-3622a-3p、miR-6813-3p、miR-4769-3p、miR-5698、miR-3184-5p、miR-1471、miR-1538、miR-449b-3p、miR-1976、miR-4268、miR-4279、miR-3620-3p、miR-3944-3p、miR-3156-3p、miR-3187-5p、miR-4685-3p、miR-4695-3p、miR-4697-3p、miR-4713-5p、miR-4723-3p、miR-371b-3p、miR-3151-3p、miR-3192-3p、miR-6728-3p、miR-6736-3p、miR-6740-3p、miR-6741-3p、miR-6743-3p、miR-6747-3p、miR-6750-3p、miR-6754-3p、miR-6759-3p、miR-6761-3p、miR-6762-3p、miR-6769a-3p、miR-6776-3p、miR-6778-3p、miR-6779-3p、miR-6786-3p、miR-6787-3p、miR-6792-3p、miR-6794-3p、miR-6801-3p、miR-6802-3p、miR-6803-3p、miR-6804-3p、miR-6810-5p、miR-6823-3p、miR-6825-3p、miR-6829-3p、miR-6833-3p、miR-6834-3p、miR-6780b-3p、miR-6845-3p、miR-6862-3p、miR-6865-3p、miR-6870-3p、miR-6875-3p、miR-6877-3p、miR-6879-3p、miR-6882-3p、miR-6885-3p、miR-6886-3p、miR-6887-3p、miR-6890-3p、miR-6893-3p、miR-6894-3p、miR-7106-3p、miR-7109-3p、miR-7114-3p、miR-7155-5p、miR-7160-5p、miR-615-3p、miR-920、miR-1825、miR-675-3p、miR-1910-5p、miR-2278、miR-2682-3p、miR-3122、miR-3151-5p、miR-3175、miR-4323、miR-4326、miR-4284、miR-3605-3p、miR-3622b-5p、miR-3646、miR-3158-5p、miR-4722-3p、miR-4728-3p、miR-4747-3p、miR-4436b-5p、miR-5196-3p、miR-5589-5p、miR-345-3p、miR-642b-5p、miR-6716-3p、miR-6511b-3p、miR-208a-5p、miR-6726-3p、miR-6744-5p、miR-6782-3p、miR-6789-3p、miR-6797-3p、miR-6800-3p、miR-6806-5p、miR-6824-3p、miR-6837-5p、miR-6846-3p、miR-6858-3p、miR-6859-3p、miR-6861-3p、miR-6880-3p、miR-7111-3p、miR-7152-5p、miR-642a-5p、miR-657、miR-1236-3p、miR-764、miR-4314、miR-3675-3p、miR-5703、miR-3191-5p、miR-6511a-3p、miR-6809-3p、miR-6815-5p、miR-6857-3p、miR-6878-3p、及びmiR-371a-5pからなる群から選択される1以上のポリヌクレオチドIの発現量を測定することを含み、
任意に、別の認知症マーカーである、miR-766-3p、miR-1229-3p、miR-1306-5p、miR-210-5p、miR-198、miR-485-3p、miR-668-3p、miR-532-3p、miR-877-3p、miR-1238-3p、miR-3130-5p、miR-4298、miR-4290、miR-3943、miR-346、及びmiR-767-3pからなる群から選択される1以上のポリヌクレオチドIIの発現量を測定することをさらに含み、
該測定された発現量を用いて、被験体が認知症に罹患しているか否かをin vitroで評価するか、又は被験体が認知症に罹患する可能性又はin vitroで予測することを含む、認知症の検出又は予測方法。 - 前記ポリヌクレオチドI又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドIの発現量の測定を行い、前記核酸が、下記の(u)~(y)のいずれかに示すポリヌクレオチド:
(u)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(v)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列を含むポリヌクレオチド、(w)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(x)配列番号3、8、15、26、34、40、53、69、99、101、107、109、112、125、128、133、191~194、212、及び250~374のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(y)前記(u)~(x)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドであり、
前記ポリヌクレオチドII又は該ポリヌクレオチドの相補鎖と特異的に結合可能な核酸を用いて前記ポリヌクレオチドIIの発現量の測定を行い、前記核酸が、下記の(p)~(t)のいずれかに示すポリヌクレオチド:
(p)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(q)配列番号375~390のいずれかで表される塩基配列を含むポリヌクレオチド、
(r)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列からなるポリヌクレオチド、その変異体、その誘導体、又は15以上の連続した塩基を含むその断片、
(s)配列番号375~390のいずれかで表される塩基配列もしくは当該塩基配列においてuがtである塩基配列に相補的な塩基配列を含むポリヌクレオチド、及び
(t)前記(p)~(s)のいずれかのポリヌクレオチドとストリンジェントな条件下でハイブリダイズするポリヌクレオチド、
からなる群から選択されるポリヌクレオチドである、請求項32に記載の方法。 - 請求項1~10のいずれか1項に記載のキット又は請求項11~22のいずれか1項に記載のデバイスを用いて、被験体の検体における標的遺伝子の発現量を測定する、請求項23~33のいずれか1項に記載の方法。
- 前記被験体が、ヒトである、請求項23~34のいずれか1項に記載の方法。
- 前記検体が、血液、血清又は血漿である、請求項23~35のいずれか1項に記載の方法。
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EP4328587A2 (en) | 2024-02-28 |
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US20210047691A1 (en) | 2021-02-18 |
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EP3754019A4 (en) | 2022-02-16 |
EP3754019B1 (en) | 2024-01-31 |
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