Bardet-biedl susceptibility gene and uses thereof
AssigneeUniversity of Iowa Research Foundation
InventorsVal C. Sheffield, Kirk Mykytyn, Edwin M. Stone
Life of this patent
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Abstract
The present invention relates to the identification of a gene, now designated BBS4, that is involved in the genetic disease Bardet Biedl Syndrome (BBS), which is characterized by such diverse symptoms as obesity, diabetes, hypertension, mental retardation, renal cancer and other abnormalities, retinopathy and hypogonadism. The human BBS4 protein disclosed herein is 519 amino acids in length and is coded for by a gene spanning 16 exons. Homologs have been identified in mouse, rat, zebrafish. Methods of use for the gene, for example in diagnosis and therapy of BBS and in drug screening, also are described.
Claims59
An isolated and purified nucleic acid encoding a human BBS4 polypeptide.
An oligonucleotide of about 10 to about 50 bases comprising at least 10 consecutive bases of SEQ ID NO:
- 1 or the complement thereof.
An isolated and purified human BBS4 polypeptide.
A method of expressing a BBS4 polypeptide comprising transforming a host cell with an expression construct encoding a BBS4 polypeptide and culturing said host cell under conditions supporting expression of said BBS4 polypeptide.
A peptide of 8 to 50 residues comprising at least 5 consecutive residues of SEQ ID NO:
- 2.
A monoclonal antibody that binds immunologically to a polypeptide comprising the sequence of SEQ ID NO:
- 2.
A hybdridoma cells that produces a monoclonal antibody that binds immunologically to a polypeptide comprising the sequence of SEQ ID NO:
- 2.
A polyclonal antiserum, antibodies of which bind immunologically to a polypeptide comprising the sequence of SEQ ID NO:
- 2
A method of diagnosing Bardet-Biedl Syndrome (BBS) comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of identifying an individual genetically predisposed to obesity comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of identifying an individual genetically predisposed to diabetes mellitus comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of identifying an individual genetically predisposed to renal defects comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of identifying an individual genetically predisposed to retinopathy comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of identifying an individual genetically predisposed to hypogonadism comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of identifying an individual genetically predisposed to polydactyly comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of identifying an individual genetically predisposed to mental retardation comprising identifying a mutation in a BBS4 polypeptide or nucleic acid.
A method of screening for a modulator of BBS4 expression comprising:
- (a) providing a cell expressing a BBS4 polypeptide;
- (b) contacting said cell with a candidate modulator;
- (c) measuring BBS4 expression;
- and
- (d) comparing said BBS4 expression in the presence of said candidate modulator with the expression of BBS4 in the absence of said candidate modulator;
- wherein a difference in the expression of BBS4 in the presence of said candidate modulator, as compared with the expression of BBS4 in the absence of said candidate modulator, identifies said candidate modulator as a modulator of BBS4 expression.
A method of screening for a modulator of BBS4 expression comprising:
- (a) providing a cell that comprises an expression construct encoding an indicator polypeptide under the control of a BBS4 polypeptide;
- (b) contacting said cell with a candidate modulator;
- (c) measuring expression of said indicator polypeptide;
- and
- (d) comparing said expression of said indicator polypeptide in the presence of said candidate modulator with the expression of said indicator polypeptide in the absence of said candidate modulator;
- wherein a difference in the expression of said indicator polypeptide in the presence of said candidate modulator, as compared with the expression of said indicator polypeptide in the absence of said candidate modulator, identifies said candidate modulator as a modulator of BBS4 expression.
A method of producing a modulator of BBS4 expression comprising:
- (a) providing a cell expressing a BBS4 polypeptide;
- (b) contacting said cell with a candidate modulator;
- (c) measuring BBS4 expression;
- (d) comparing said BBS4 expression in the presence of said candidate modulator with the expression of BBS4 in the absence of said candidate modulator;
- wherein a difference in the expression of BBS4 in the presence of said candidate modulator, as compared with the expression of BBS4 in the absence of said candidate modulator, identifies said candidate modulator as a modulator of BBS4 expression;
- and
- (e) producing the modulator.
A modulator of BBS4 expression produced according to the method comprising:
- (a) providing a cell expressing a BBS4 polypeptide;
- (b) contacting said cell with a candidate modulator;
- (c) measuring BBS4 expression;
- (d) comparing said BBS4 expression in the presence of said candidate modulator with the expression of BBS4 in the absence of said candidate modulator;
- wherein a difference in the expression of BBS4 in the presence of said candidate modulator, as compared with the expression of BBS4 in the absence of said candidate modulator, identifies said candidate modulator as a modulator of BBS4 expression;
- and
- (e) producing the modulator.
Dependencies are inferred from the claim text.