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RU2341795C2 - Genes related to dogs osteoarthritis and method and compositions related to it - Google Patents

Genes related to dogs osteoarthritis and method and compositions related to it Download PDF

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RU2341795C2
RU2341795C2 RU2006131570/15A RU2006131570A RU2341795C2 RU 2341795 C2 RU2341795 C2 RU 2341795C2 RU 2006131570/15 A RU2006131570/15 A RU 2006131570/15A RU 2006131570 A RU2006131570 A RU 2006131570A RU 2341795 C2 RU2341795 C2 RU 2341795C2
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expression
osteoarthritis
genes
seq
sample
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RU2006131570A (en
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Рондо П. МИДДЛТОН (US)
Рондо П. МИДДЛТОН
Стивен С. ХАННА (US)
Стивен С. ХАННА
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Нестек С.А.
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    • C—CHEMISTRY; METALLURGY
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    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
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    • 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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    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/136—Screening for pharmacological compounds
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    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers

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  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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Abstract

FIELD: molecular biology.
SUBSTANCE: combination is described that contains molecules of polynucleotides selected from the group SEQ ID NO 1:396, which are exposed to differential expression during osteoarthritis. Methods are also described, which may be used for diagnostics and prognostication of osteoarthritis, and also methods that might be used for screening of tested substances for efficiency in possible methods of osteoarthritis therapy.
EFFECT: identification of sequences of nucleic acids that are exposed to differential expression at the subject.
15 cl, 7 ex, 23 tbl, 2 dwg

Description

Текст описания приведен в факсимильном виде.

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The text of the description is given in facsimile form.
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Claims (14)

1. Комбинация, включающая множество молекул полинуклеотидов, причем молекулы полинуклеотидов дифференциально экспрессируются у субъектов, страдающих остеоартритом или в предостеоартритном состоянии, по сравнению с экспрессией у субъектов, не страдающих остеоартритом или не в предостеоартритном состоянии, в которой множество молекул полинуклеотидов включает две или больше молекул, выбранных из SEQ ID NO:1-396.1. A combination comprising a plurality of polynucleotide molecules, the polynucleotide molecules being differentially expressed in subjects suffering from osteoarthritis or in a pre-arthritic state, as compared to expression in subjects not suffering from osteoarthritis or not in a pre-arthritic state in which the plurality of polynucleotide molecules includes two or more molecules selected from SEQ ID NO: 1-396. 2. Способ выявления дифференциальной экспрессии нуклеиновых кислот в образце, включающий стадии2. A method for detecting differential expression of nucleic acids in a sample, comprising the steps of a) гибридизации комбинации, включающей множество молекул полинуклеотидов, причем молекулы полинуклеотидов дифференциально экспрессируются у субъектов, страдающих остеоартритом или в предостеоартритном состоянии, по сравнению с экспрессией у субъектов, не страдающих остеоартритом или не в предостеоартритном состоянии, с нуклеиновыми кислотами образца, образуя таким образом один или несколько гибридизационных комплексов, где молекулы полинуклеотидов гибридизуются с последовательностями нуклеиновых кислот, выбранными из SEQ ID NO: 1-396;a) hybridization of a combination comprising a plurality of polynucleotide molecules, the polynucleotide molecules being differentially expressed in subjects suffering from osteoarthritis or in a pre-arthritic state, compared with expression in subjects not suffering from osteoarthritis or not in a pre-arthritic state, with the nucleic acids of the sample, thus forming one or several hybridization complexes, where polynucleotide molecules hybridize to nucleic acid sequences selected from SEQ ID NO: 1-396; b) детектирования гибридизационных комплексов; иb) detecting hybridization complexes; and c) сравнения гибридизационных комплексов с таковыми для стандарта, при этом различия между гибридизационными комплексами стандарта и образца указывают на дифференциальную экспрессию нуклеиновых кислот в образце.c) comparing hybridization complexes with those of the standard, the differences between the hybridization complexes of the standard and the sample indicate differential expression of nucleic acids in the sample. 3. Способ по п.2, дополнительно включающий стадию обработки образца тестируемым соединением, причем сравнение со стандартом указывает на то, изменяет ли обработка тестируемым соединением дифференциальную экспрессию нуклеиновых кислот или полипептидов в образце.3. The method according to claim 2, further comprising the step of treating the sample with the test compound, the comparison with the standard indicating whether treatment with the test compound changes the differential expression of nucleic acids or polypeptides in the sample. 4. Композиция веществ, включающая набор из двух или больше зондов для детектирования экспрессии генов, дифференциально экспрессируемых у субъектов, страдающих остеоартритом или в предостеоартритном состоянии, по сравнению с субъектами, не страдающими остеоартритом или не в предостеоартритном состоянии, причем зонды включают две или больше из молекул нуклеиновых кислот, которые специфически гибридизуются с двумя или больше генами, где гены включают SEQ ID NO: 1-396.4. A composition of substances comprising a set of two or more probes for detecting the expression of genes differentially expressed in subjects suffering from osteoarthritis or in a pre-arthritic state, compared with subjects not suffering from osteoarthritis or not in a pre-arthritic state, wherein the probes include two or more of nucleic acid molecules that specifically hybridize to two or more genes, where the genes include SEQ ID NO: 1-396. 5. Устройство для детектирования экспрессии множества генов, дифференциально экспрессирующихся при остеоартрите, включающее подложку, на которой фиксировано в известных местах множество зондов, причем зонды включают множество олигонуклеотидов или полинуклеотидов, каждый из которых специфически гибридизуется с другой последовательностью, выбранной из числа SEQ ID NO: 1-396.5. A device for detecting the expression of multiple genes differentially expressed in osteoarthritis, including a substrate on which a plurality of probes are fixed in known places, the probes comprising a plurality of oligonucleotides or polynucleotides, each of which specifically hybridizes to a different sequence selected from SEQ ID NO: 1-396. 6 Способ измерения эффекта тестируемого соединения на экспрессию одного или нескольких генов, дифференциально экспрессирующихся при остеоартрите, включающий стадии6 A method for measuring the effect of a test compound on the expression of one or more genes differentially expressed in osteoarthritis, comprising the steps of a) измерения стандартной экспрессии путем измерения продуктов транскрипции одного или нескольких генов, включающих любые из SEQ ID NO: 1-396, в стандартном образце в отсутствии тестируемого соединения;a) measuring standard expression by measuring the transcription products of one or more genes, including any of SEQ ID NOS: 1-396, in a standard sample in the absence of a test compound; b) измерения опытной экспрессии путем измерения продуктов транскрипции одного или нескольких генов, включающих любые из SEQ ID NO: 1-396 в опытном образце в присутствии тестируемого соединения;b) measuring the experimental expression by measuring the transcription products of one or more genes, including any of SEQ ID NOS: 1-396 in a test sample in the presence of a test compound; c) сравнения стандартной экспрессии с опытной экспрессией, причем изменение опытной экспрессии по сравнению со стандартной экспрессией указывает на эффект тестируемого соединения на экспрессию генов, дифференциально экспрессирующихся при остеоартрите, по сравнению с состоянием без остеоартрита.c) comparing standard expression with experimental expression, wherein a change in experimental expression compared to standard expression indicates the effect of the test compound on the expression of genes differentially expressed in osteoarthritis compared with a condition without osteoarthritis. 7. Способ по п.6, в котором при измерении используют композицию веществ, включающую множество зондов, причем зонды включают два или больше генов, включающих любые из SEQ ID NO: 1-396.7. The method according to claim 6, in which when measuring use a composition of substances comprising many probes, and the probes include two or more genes, including any of SEQ ID NO: 1-396. 8. Способ по п.6, в котором стандартный и опытный образцы получают из, по меньшей мере, одного субъекта-млекопитающего.8. The method according to claim 6, in which standard and experimental samples are obtained from at least one mammalian subject. 9. Способ диагностики или составления прогноза для субъекта, проявляющего признаки остеоартрита, (OA) включающий9. A method for diagnosing or making a prognosis for a subject exhibiting signs of osteoarthritis, (OA) comprising a) получение образца от субъекта;a) obtaining a sample from the subject; b) измерение в образце продукции продуктов транскрипции, образующихся при экспрессии одного или нескольких связанных с OA генов, включающих любые из SEQ ID NO: 1-396;b) measuring in a production sample transcription products resulting from the expression of one or more OA-related genes, including any of SEQ ID NO: 1-396; c) сравнение продуктов транскрипции образца с таковыми для стандарта, причем отличие в экспрессии любого из связанных с OA генов указывает на остеоартрит.c) comparing the transcription products of the sample with those of the standard, the difference in the expression of any of the OA-related genes indicating osteoarthritis. 10. Набор для выявления наличия остеоартрита или предрасположенности к остеоартриту у субъекта, включающий один или несколько олигонуклеотидов, содержащих, по меньшей мере, 10 следующих друг за другом нуклеотидов из последовательности, выбранной из последовательностей, гибридизующихся с двумя или более генами, включающими любые из SEQ ID NO: 1-396, причем олигонуклеотиды специфически связываются с нуклеиновыми кислотами, дифференциально экспрессирующимися у субъектов, страдающих остеоартритом или предрасположенных к нему, по сравнению с экспрессией у субъектов, не страдающих остеоартритом или не предрасположенных к нему.10. A kit for detecting the presence of osteoarthritis or a predisposition to osteoarthritis in a subject, comprising one or more oligonucleotides containing at least 10 consecutive nucleotides from a sequence selected from sequences hybridizing to two or more genes including any of SEQ ID NO: 1-396, wherein the oligonucleotides specifically bind to nucleic acids differentially expressed in subjects suffering from or predisposed to osteoarthritis, compared to exp recession in subjects not suffering from osteoarthritis or not predisposed to it. 11. Набор для определения экспрессии генов, дифференциально экспрессирующихся при остеоартрите, включающий контейнер, содержащий набор из двух или больше зондов, причем зонды включают один или более из олигонуклеотидов или полинуклеотидов, специфически гибридизующихся с двумя или более генами, включающими любые из SEQ ID NO: 1-396; а также инструкции по проведению анализа экспрессии генов.11. A kit for determining the expression of genes differentially expressed in osteoarthritis, comprising a container containing a set of two or more probes, the probes include one or more of oligonucleotides or polynucleotides that specifically hybridize with two or more genes, including any of SEQ ID NO: 1-396; and instructions for analyzing gene expression. 12. Способ модулирования экспрессии связанных с остеоартритом генов в клетке путем введения эффективного количества соединения в соответствующих условиях с тем, чтобы повлиять на экспрессию, по меньшей мере, одного связанного с остеоартритом гена, имеющего последовательность, выбранную из SEQ ID NO: 1-396.12. A method of modulating the expression of osteoarthritis-related genes in a cell by administering an effective amount of a compound under appropriate conditions so as to affect the expression of at least one osteoarthritis-related gene having a sequence selected from SEQ ID NO: 1-396. 13. Способ по п.12, в котором соединение представляет собой витамин, минерал, нутрицевтик, низкомолекулярное фармацевтическое средство, белок, полипептид, нуклеиновую кислоту, жирную кислоту или полисахарид.13. The method according to item 12, in which the compound is a vitamin, mineral, nutraceutical, low molecular weight pharmaceutical agent, protein, polypeptide, nucleic acid, fatty acid or polysaccharide. 14. Способ по п.13, в котором соединение представляет собой эйкозапентаеновую кислоту, арахидоновую кислоту, глюкозамин, хондроитинсульфат, 1α,25-дигидроксивитамин D3 или 24R,25-дигидроксивитамин D3.14. The method according to item 13, in which the compound is eicosapentaenoic acid, arachidonic acid, glucosamine, chondroitin sulfate, 1α, 25-dihydroxyvitamin D 3 or 24R, 25-dihydroxyvitamin D 3 . 15. Способ идентификации соединений, модулирующих связанные с остеоартритом гены, включающий15. A method for identifying compounds modulating genes associated with osteoarthritis, including a) измерение стандартной экспрессии путем измерения продуктов транскрипции одного или нескольких генов, включающих любые из SEQ ID NO: 1-396, в стандартном образце в отсутствие тестируемого соединения;a) measuring standard expression by measuring the products of transcription of one or more genes, including any of SEQ ID NO: 1-396, in a standard sample in the absence of a test compound; b) измерение опытной экспрессии путем измерения продуктов транскрипции одного или нескольких генов, включающих любые из SEQ ID NO: 1-396, в опытном образце в присутствии тестируемого соединения; иb) measuring the experimental expression by measuring the transcription products of one or more genes, including any of SEQ ID NOS: 1-396, in a test sample in the presence of a test compound; and c) сравнение стандартной экспрессии с опытной экспрессией, причем изменение опытной экспрессии по сравнению со стандартной экспрессией указывает на эффект тестируемого соединения на экспрессию генов, дифференциально экспрессирующихся при остеоартрите, по сравнению с состоянием без остеоартрита.c) comparing standard expression with experimental expression, wherein a change in experimental expression compared to standard expression indicates the effect of the test compound on the expression of genes differentially expressed in osteoarthritis compared with a condition without osteoarthritis.
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