Compositions and methods for diagnostics and therapeutics for hydrocephalus
AssigneeThe United States of America, as represented by the Secretary, Department of Health and Human Services
InventorsPerry J. Blackshear, Deborah J. Stumpo, Darryl C. Zeldin, Joan P. Graves
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to RFX4_v3 protein and nucleic acids encoding the RFX4_v3 protein. The present disclosure provides non-human transgenic animals with altered RFX4_v3 genes, and provides assays for the detection of RFX4_v3 and RFX4_v3 polymorphisms associated with disease states. The present disclosure additionally provides methods of determining a subjects' risk of developing congenital hydrocephalus, and treating or inhibiting its development.
Claims31
An isolated nucleic acid molecule encoding a RFX4_v3 polypeptide, wherein the polypeptide comprises:
- a) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
- 8;
- b) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:
- 8, wherein fourteen consecutive amino acids within the N-terminal sequence of the polypeptide are identical to residues 1-14 of SEQ ID NO:
- 8;
- or
- c) the amino acid sequence of SEQ ID NO:
- 8,
- wherein the polypeptide in a), b), or c) has RFX4_v3 activity.
An isolated nucleic acid molecule encoding a RFX4_v3 polypeptide, comprising (i) a nucleic acid sequence at least 99% identical to the nucleic acid sequence of SEQ ID NO:
- 37, or (ii) a nucleic acid sequence at least 95% identical to the nucleic acid sequence of SEQ ID NO:
- 38 or SEQ ID NO:
- 39.
An isolated nucleic acid molecule that hybridizes under conditions of high stringency to a polynucleotide consisting of nucleotides 1-42 of a nucleic acid sequence selected from the group consisting of SEQ ID NO:
- 37, SEQ ID NO:
- 38, and SEQ ID NO:
- 39, wherein the isolated nucleic acid molecule comprises at least 20 contiguous nucleotides of nucleotides 1-42 of SEQ ID NO:37, SEQ ID NO:
- 38, or SEQ ID NO:
- 39, and wherein the isolated nucleic acid molecule encodes a RFX4_v3 polypeptide at least 99% identical to the amino acid sequence of SEQ ID NO:
- 8, SEQ ID NO:
- 6, or SEQ ID NO:
- 10, respectively.
An isolated nucleic acid molecule comprising a nucleic acid sequence encoding a RFX4_v3 polypeptide comprising SEQ ID NO:
- 6, SEQ ID NO:
- 8, or SEQ ID NO:
- 10.
A method for producing a variant RFX4_v3 polypeptide, wherein the method comprises:
- mutagenizing a wild-type nucleic acid sequence having SEQ ID NO:
- 37;
- expressing the mutagenized nucleic acid sequence;
- and
- screening the variant RFX4_v3 polypeptide for a RFX4_v3 activity, wherein the variant RFX4_v3 polypeptide comprises:
- a) an amino acid sequence at least 99% identical to the amino acid sequence of SEQ ID NO:
- 8;
- b) an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO:8, wherein fourteen consecutive amino acids within the N-terminal sequence of the polypeptide are identical to residues 1-14 of SEQ ID NO:
- 8;
- or
- c) the amino acid sequence of SEQ ID NO:
- 8,
- wherein the polypeptide in a), b), or c) has RFX4_v3 activity.
A method for detecting a polynucleotide molecule in a biological sample, comprising:
- hybridizing the polynucleotide molecule in the biological sample to an isolated nucleic acid molecule comprising the sequence of SEQ ID NO:
- 37, SEQ ID NO:
- 38, or SEQ ID NO:
- 39, to produce a hybridization complex, wherein the polynucleotide molecule hybridizes under conditions of high stringency to nucleotides 1-42 of SEQ ID NO:
- 37, SEQ ID NO:
- 38, or SEQ ID NO:
- 39;
- detecting the hybridization complex, wherein the presence of the hybridization complex indicates the presence of the polynucleotide molecule encoding RFX4_v3 in the biological sample, thereby detecting the polynucleotide molecule in the biological sample.
An isolated nucleic acid molecule encoding a RFX4_v3 polypeptide having RFX4_v3 activity, wherein the polypeptide comprises SEQ ID NO:
- 8.
An isolated nucleic acid molecule encoding a RFX4_v3 polypeptide having RFX4_v3 activity, wherein the isolated nucleic acid molecule comprises SEQ ID NO:
- 37.
An isolated nucleic acid molecule encoding a RFX4_v3 polypeptide, consisting of the nucleic acid sequence of SEQ ID NO:
- 37, SEQ ID NO:
- 38, or SEQ ID NO:
- 39.
Dependencies are inferred from the claim text.