Genetic mutation underlying orthostatic intolerance and diagnostic and therapeutic methods relating thereto
AssigneeVanderbilt University
InventorsDavid Robertson, Randy D. Blakely
Life of this patent
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Abstract
Isolated polynucleotide molecules and peptides encoded by these molecules are used in the analysis of human norepinephrine (NE) transporter variants, as well as in diagnostic and therapeutic applications, relating to a human NE transporter polymorphism. By analyzing genomic DNA or amplified genomic DNA, or amplified cDNA derived from mRNA, it is possible to type a human NE transporter with regard to the human NE transporter polymorphism, for example, in the context of diagnosing and treating NE transport impairments, and disorders associated with NE transport impairments, such as orthostatic intolerance.
Claims79
A method of screening for susceptibility to sub-optimal norepinephrine (NE) transport in a subject, the method comprising:
- (a) obtaining a biological sample from the subject;
- and
- (b) detecting a polymorphism of a NE transporter gene in a biological sample from the subject, the presence of the polymorphism indicating the susceptibility of the subject to sub-optimal norepinephrine transport.
An oligonucleotide pair, wherein a first oligonucleotide of the pair hybridizes to a first portion of the NE transporter gene, wherein the first portion includes a polymorphism of the NE transporter gene, and wherein the second of the oligonucleotide pair hybridizes to a second portion of the NE transporter gene that is adjacent to the first portion.
A set of oligonucleotide primers comprising an anti-sense primer and a sense primer, wherein said oligonucleotide primer set is suitable for amplifying a portion of the NE transporter gene, wherein the portion includes a polymorphism of the NE transporter gene.
A kit for detecting a polymorphism in a gene encoding a NE transporter in a subject, the kit comprising:
- (a) a reagent for detecting the presence of a polymorphism of NE transporter gene in a nucleic acid sample from the subject;
- and
- (b) a container for the reagent.
An isolated and purified biologically active human NE transporter polypeptide having an alanine to proline transversion in a transmembrane domain of the polypeptide.
An isolated and purified nucleic acid molecule which encodes a biologically active human NE transporter polypeptide having an alanine to proline transversion in a transmembrane domain of the polypeptide.
A method for detecting an antibody or fragment thereof, in a sample suspected of containing an antibody or fragment thereof, the method comprising:
- (a) contacting the sample with a binding substance comprising a NE transporter polypeptide under conditions favorable to binding of an antibody or fragment thereof to the binding substance to form a complex therebetween;
- and
- (b) detecting the complex via a label conjugated to the binding substance or via a labeled reagent that specifically binds to the complex subsequent to its formation.
An assay kit for detecting the presence, in a biological sample, of an antibody immunoreactive with a NE transporter polypeptide, the kit comprising a first container containing a NE transporter polypeptide that immunoreacts with the antibody, with the polypeptide present in an amount sufficient to perform at least one assay.
A method to enhance transport of NE in a vertebrate subject, the method comprising introducing to a tissue in said vertebrate subject associated with transport of NE a construct comprising a nucleic acid sequence encoding a NE transporter gene product operatively linked to a promoter, wherein production of the NE transporter gene product in the tissue results in enhanced transport of NE.
A method for detection of impaired norepinephrine (NE) transport function in a vertebrate subject, the method comprising:
- (a) performing a diagnostic test on the subject wherein the diagnostic test is associated with evaluation of NE transport in the subject;
- (b) comparing data from the test performed in step (a) to reference data from a reference subject known to have deficient NE transport;
- and
- (c) detecting impaired NE transport in the vertebrate subject if the data from the test subject corresponds to the data from the reference subject.
Dependencies are inferred from the claim text.