Gene linked to osteoarthritis
AssigneedeCODE Genetics ehf.
InventorStefan E. Stefansson
Life of this patent
Estimating the term…
Abstract
A role of the human MATN3 gene in osteoarthritis is disclosed. Methods for diagnosis, prediction of clinical course and treatment for osteoarthritis using polymorphisms in the MATN3 gene are also disclosed.
Claims56
An isolated nucleic acid molecule comprising a matrilin-3 gene, or a fragment or variant thereof, the nucleotide sequence of SEQ ID NO:
- 1 and comprising at least one polymorphism as shown in Table 3 or FIGS. 5A-5C.
A nucleic acid encoding a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2, 3, 4, 5, 6, 7, 8 and 9.
A method for assaying the presence of a first nucleic acid molecule in a sample, comprising contacting said sample with a second nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of SEQ ID NO:
- 1 comprising at least one polymorphism as shown in Table 3 or FIGS. 5A-5C and complements thereof, under high stringency conditions.
A vector comprising an isolated nucleic acid molecule selected from the group consisting of:
- SEQ ID NO:
- 1 and comprising at least one polymorphism shown in Table 3 or FIGS. 5A-5C, and complements thereof, operatively linked to a regulatory sequence.
An isolated polypeptide encoded by a matrilin-3 gene, wherein the matrilin-3 gene has the sequence of SEQ ID NO:
- 1 comprising at least one polymorphism as shown in Table 3 or FIGS. 5A-5C, or complements thereof.
An antibody, or an antigen-binding fragment thereof, which selectively binds to an amino acid sequence selected from the group consisting of SEQ ID NOs:
- 2-9, or to a fragment or variant of said amino acid sequence.
A method of diagnosing a susceptibility to osteoarthritis in an individual, comprising detecting a polymorphism in a matrilin-3 gene, wherein the presence of the polymorphism in the gene is indicative of a susceptibility to osteoarthritis.
A method of diagnosing a susceptibility to osteoarthritis, comprising detecting an alteration in the expression or composition of a polypeptide encoded by a matrilin-3 gene in a test sample, in comparison with the expression or composition of a polypeptide encoded by matrilin-3 gene in a control sample, wherein the presence of an alteration in expression or composition of the polypeptide in the test sample is indicative of a susceptibility to osteoarthritis.
A method of identifying an agent which alters expression of a matrilin-3 gene, comprising the steps of:
- a) contacting a solution containing a nucleic acid comprising the promoter region of matrilin-3 gene operably linked to a reporter gene, with an agent to be tested;
- b) assessing the level of expression of the reporter gene;
- and
- c) comparing the level of expression with a level of expression of the reporter gene in the absence of the agent,
- wherein if the level of expression of the reporter gene in the presence of the agent differs, by an amount that is statistically significant, from the level of expression in the absence of the agent, then the agent is an agent that alters expression of a matrilin-3 gene.
A method of identifying a polypeptide which interacts with a matrilin-3 gene polypeptide, comprising employing a yeast two-hybrid system using a first vector which comprises a nucleic acid encoding a DNA binding domain and a matrilin-3 gene polypeptide, splicing variant, fragment or derivative thereof, and a second vector which comprises a nucleic acid encoding a transcription activation domain and a nucleic acid encoding a test polypeptide, wherein if transcriptional activation occurs in the yeast two-hybrid system, the test polypeptide is a polypeptide which interacts with a matrilin-3 polypeptide.
A matrilin-3 gene therapeutic agent selected from the group consisting of:
- a matrilin-3 gene or fragment or derivative thereof;
- a polypeptide encoded by matrilin-3 gene;
- a matrilin-3 gene receptor;
- a matrilin-3 gene binding agent;
- a peptidomimetic;
- a fusion protein;
- a prodrug;
- an antibody;
- an agent that alters matrilin-3 gene expression;
- an agent that alters activity of a polypeptide encoded by matrilin-3 gene;
- an agent that alters posttranscriptional processing of a polypeptide encoded by matrilin-3 gene;
- an agent that alters interaction of a matrilin-3 gene with a matrilin-3 gene binding agent;
- an agent that alters transcription of splicing variants encoded by matrilin-3 gene;
- and a ribozyme.
A method of treating osteoarthritis in an individual, comprising administering a matrilin-3 gene therapeutic agent to the individual, in a therapeutically effective amount.
A transgenic animal comprising a nucleic acid selected from the group consisting of:
- an exogenous matrilin-3 gene and a nucleic acid encoding a matrilin-3 gene polypeptide.
A method for assaying a sample for the presence of a matrilin-3 gene nucleic acid, comprising:
- a) contacting said sample with a nucleic acid comprising a contiguous nucleotide sequence, which is a at least partially complementary to a part of the sequence of said matrilin-3 gene nucleic acid under conditions suitable for hybridization, and
- b) assessing whether hybridization has occurred between a matrilin-3 gene nucleic acid and said nucleic acid comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the sequence of said matrilin-3 gene nucleic acid.
A reagent for assaying a sample for the presence of a matrilin-3 gene nucleic acid, said reagent comprising a nucleic acid comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the nucleotide sequence of said matrilin-3 gene nucleic acid.
A reagent kit for assaying a sample for the presence of a matrilin-3 gene nucleic acid comprising in separate containers:
- a) one or more labeled nucleic acids comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the nucleotide sequence of said matrilin-3 gene nucleic acid;
- and
- b) reagents for detection of said label.
A reagent kit for assaying a sample for the presence of a matrilin-3 gene nucleic acid comprising one or more nucleic acids comprising a contiguous nucleotide sequence which is at least partially complementary to a part of the nucleotide sequence of said matrilin-3 gene nucleic acid, and which is capable of acting as a primer for said matrilin-3 gene nucleic acid when maintained under conditions for primer extension.
A method of diagnosing susceptibility to osteoarthritis in an individual, comprising screening for an at-risk haplotype in the matrilin-3 gene that is more frequently present in an individual susceptible to osteoarthritis compared to a healthy individual, wherein the at-risk haplotype increases risk of osteoarthritis significantly.
A method of diagnosing susceptibility to osteoarthritis in an individual, comprising screening for an at-risk haplotype in the matrilin-3 gene that is more frequently present in an individual susceptible to osteoarthritis (affected), compared to the frequency of its presence in a healthy individual (control), wherein the presence of the at-risk haplotype is indicative of a susceptibility to osteoarthritis.
A kit for diagnosing susceptibility to osteoarthritis in an individual comprising:
- primers for nucleic acid amplification of a region of the matrilin-3 gene comprising an at-risk haplotype, wherein the primers comprise a segment of nucleic acids of length suitable for nucleic acid amplification, selected from the group consisting of:
- a polymorphism at nucleic acid position 58162, 57927, 56822, 47929, 45434, 45317, 45178 and 45010, relative to SEQ ID NO:
- 1 and combinations thereof.
Dependencies are inferred from the claim text.