Juvenile hemochromatosis gene (hfe2a), expression products and uses thereof
OwnerMark Samuels, Erwin Ludwig +5inventors
InventorsMark Samuels, Erwin Ludwig, Marcia MacDonald, Patrick Franchini, Yigal Goldberg, Rajender Kamboj, George Papanikolaou
Life of this patent
Estimating the term…
Abstract
Polynucleotide and polypeptide sequences for HFE2A, as well as mutations associated with juvenile hemochromatosis, and methods of utilizing these for the screening and identification of agents for the treatment of diseases of iron metabolism, including small organic compounds, are disclosed along with methods of treating and/or ameliorating diseases of iron metabolism, especially in human patients are disclosed. Diagnostic compounds, kits and methods using HFE2A are also described.
Claims117
A method for identifying an agent that modulates HFE2A gene expression, comprising:
- (a) contacting a test compound with a genetic construct comprising a reporter gene operably linked to an HFE2A promoter under conditions supporting expression of said reporter gene;
- (b) determining a change in expression of said reporter gene as a result of said contacting,
- wherein a change in expression identifies said test compound as an agent that modulates HFE2A gene expression.
A method for identifying an agent that modulates HFE2A gene expression, comprising:
- a) contacting a test compound with a cell expressing an HFE2A gene;
- b) determining a change in expression of said HFE2A gene as a result of said contacting,
- wherein a change in expression identifies said test compound as an agent that modulates HFE2A gene expression.
A method for identifying an agent that modulates the activity of an HFE2A polypeptide, comprising:
- a) contacting a test compound with an HFE2A polypeptide under conditions supporting an activity of said polypeptide;
- and
- b) determining a change in said activity of said polypeptide as a result of said contacting,
- wherein a change in the activity identifies said test compound as an agent that modulates the activity of an HFE2A polypeptide.
A method for treating a disorder comprising administering to an animal afflicted therewith a therapeutically effective amount of an HFE2A modulator.
A method for preventing a disorder comprising administering to an animal, at risk of developing said disorder, a therapeutically effective amount of an HFE2A modulator.
A method to diagnose individuals affected by or at risk of developing a disease of iron metabolism comprising determining a mutation or polymorphism in the nucleic acid sequence of the HFE2A gene in said individual wherein said mutation or polymorphism in said gene identifies said individual as being affected by or at risk of developing a disease of iron metabolism.
A method to diagnose individuals affected by or at risk of developing a disease of iron metabolism comprising determining a mutation or polymorphism in the amino acid sequence of HFE2A polypeptide in said individual wherein a mutation or polymorphism of said HFE2A polypeptide identifies said individual as being affected by or at risk of developing a disease of iron metabolism.
A method to diagnose individuals affected by or at risk of developing a disease of iron metabolism comprising determining a decrease change in level or amount of an HFE2A polypeptide in said individual wherein said decreare chance identifies said individual as being affected by or at risk of developing a disease of iron metabolism.
A method for identifying a compound capable of modulating a HFE2A activity, comprising:
- (a) contacting a test compound with a cell that expresses HFE2A;
- and (b) assaying the ability of said test compound to modulate the transcription of a HFE2A nucleic acid or the activity of HFE2A polypeptide, thereby identifying a compound capable of modulating a HFE2A activity.
An isolated polynucleotide comprising a polynucleotide having a nucleotide sequence with at least 60 percent identity to a sequence selected from the group consisting of SEQ ID NO:
- 1, 2, 3, 4, 5, 6, 7, 8, 9, 19, 20, 21 and 22.
An isolated polypeptide comprising a polypeptide having an amino acid sequence with at least 90 percent identity to an amino acid sequence selected from the group consisting of SEQ ID NO:
- 10, 11, 12, 23, 24, 25, 26, 27 and 28.
A method for producing test data with respect to the modulation of HFE2A gene expression by a compound, comprising:
- (a) a genetic construct comprising a reporter gene operably linked to an HFE2A promoter under conditions supporting expression of said reporter gene;
- (b) determining a change in expression of said reporter gene as a result of said contacting, wherein said change shows modulation, and
- (c) producing test data with respect to the gene modulating activity of said test compound based on a change in expression of the determined genes indicating gene modulating activity.
A method for producing test data with respect to the modulation of an HFE2A polypeptide activity by a compound, comprising:
- (a) contacting a test compound with an HFE2A polypeptide under conditions promoting an activity of said HFE2A polypeptide;
- (b) determining a change in activity of said polypeptide as a result of said contacting, wherein said change shows modulation, and
- (c) producing test data with respect to the HFE2A polypeptide modulating activity of said test compound based on a change in an HFE2A polypeptide activity indicating modulating activity.
An isolated polypeptide, or fragments thereof, wherein said polypeptide comprises an amino acid sequence with at least 90 percent identity to an amino acid sequence selected from the group consisting of SEQ ID NO:
- 10, 11 and 12 and wherein said fragment comprises at least ten amino acid residues.
A method for diagnosing anemia of chronic disease comprising determining a change in level or amount of an HFE2A polypeptide in said individual wherein said change identifies said individual as being affected by or at risk of developing anemia of chronic disease.
A method for diagnosing iron-deficiency anemia comprising determining a change in level or amount of an HFE2A polypeptide in said individual wherein said change identifies said individual as being affected by or at risk of developing iron-deficiency anemia.
Dependencies are inferred from the claim text.