Gene and sequence variation associated with lipid disorder

• US 20030064372A1
• Filed: 09/07/2001
• Published: 04/03/2003
• Est. Priority Date: 06/22/2000
• Status: Abandoned Application

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Lusis, Aldons JAKE, Ross, David, Bodnar, Jackie S., Chatterjee, Aurobindo, Ohmen, Jeff, Tafuri, Sherrie, Castellani, Lawrence W., Jong, Pieter de, Wu, Chenyan
• Application Number:
  US09/949,428
• Publication Number:
  US 20030064372A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/156 Polymorphic or mutational markers
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

The present invention relates to the discovery of gene and its sequence variation associated with lipid disorder and cancer. The present invention also relates to the study of metabolic pathways and cellular mechanisms to identify other genes, receptors, and relationships that contribute to lipid disorder and cancer. The present invention also relates to germline or somatic sequence variation and its use in the diagnosis and prognosis of predisposition to lipid disorder and cancer. The present invention also provides primers or probes specific for the detection and analysis of such sequence variation. The present invention also relates to methods to screen drugs for inhibition or restoration of gene function as an anti-lipid disorder or anti-cancer therapy. Finally, the present invention relates to other anti-lipid disorder or anti-cancer therapies, such as gene therapy, protein replacement therapy, etc.

Claims

1. An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of:

(a) a sequence variation of SEQ ID NO;

1, wherein said variation is associated with a lipid disorder;

(b) a complementary sequence of (a);

(c) a polynucleotide sequence having at least 65% sequence identity to sequence of (a); and

(d) a complementary sequence of (c).

4. The polynucleotide of claim 1 or 3 wherein said variation is a mutation.

5. The polynucleotide of claim 1 or 3 wherein said variation is a polymorphism.

8. An isolated polynucleotide having at least 12 contiguous nucleotides of the polynucleotides of claim 1 or 3 wherein said 12 contiguous nucleotides span said variation position.

10. A polynucleotide specific for the HYPLIP1 locus wherein said polynucleotide hybridizes, under stringent conditions, to at least 12 contiguous nucleotides of the polynucleotide of claim 1 or 2.

11. The polynucleotide according to claim 10 wherein said polynucleotide is selected from the group consisting of SEQ ID NOs:

23-406.

17. A method for analyzing a polynucleotide in a sample comprising the steps of:

(a) contacting a polynucleotide in a sample with a probe wherein said probe hybridizes to the polynucleotides of claim 1 or 3 to form a hybridization complex; and

(b) detecting the hybridization complex.

20. An expression vector comprising the polynucleotide of claim 1 or 3.

21. A host cell comprising the expression vector of claim 20.

22. A method of producing a polypeptide comprising culturing the host cells of claim 21 and recovering the polypeptide from the host cell.

2. An isolated polynucleotide comprising a sequence variation of SEQ ID NO:

2 or its complementary sequence, wherein said variation is associated with a lipid disorder.

3. An isolated polynucleotide comprising a polynucleotide sequence selected from the group consisting of:

(a) a sequence variation of SEQ ID NO;

4, wherein said variation is associated with a lipid disorder;

(b) a complementary sequence of (a);

(c) a polynucleotide sequence having at least 65% sequence identity to sequence of (a); and

(d) a complementary sequence of (c).

12. A polynucleotide specific for the FCHL1 locus wherein said polynucleotide that hybridizes, under stringent conditions, to at least 12 contiguous nucleotides of the polynucleotide of claim 3.

13. The polynucleotide of claim 12 wherein said polynucleotide is selected from the group consisting of SEQ ID NOs:

6-22.

14. A kit for the detection of the FCHL1 locus comprising a polynucleotide of claim 12 and instructions relating to detection.

18. A method for analyzing the expression of FCHL1 comprising the steps of (a) contacting a sample with a probe wherein said probe comprises the polynucleotide of claim 12;

and

(b) detecting the expression of FCHL1 mRNA transcript in said sample.

23. A pharmaceutical composition comprising

(a) the polynucleotide of claim 3, the polypeptide of claim 7, or an isolated antibody which is immunoreactive to the polypeptide of claim 7;

and

(b) a suitable pharmaceutical carrier.

24. A method for treating or preventing a lipid disorder associated with expression of FCHL1, wherein said method comprising administering to a subject an effective amount of the pharmaceutical composition of claim 23.

6. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:

(a) a variant form of SEQ ID NO;

3, wherein said variant form is associated with a lipid disorder; and

(b) an amino acid sequence having at least 65% sequence identity to sequence of (a).

9. An isolated polypeptide having at least four contiguous amino acids of the polypeptides of claim 6 or 7 wherein said four contiguous amino acids span said variant position.

15. An isolated antibody which is immunoreactive to the polypeptide of claim 6 or 7.

7. An isolated polypeptide comprising an amino acid sequence selected from the group consisting of:

(a) a variant form of SEQ ID NO;

5, wherein said variant form is associated with a lipid disorder; and

(b) an amino acid sequence having at least 65% sequence identity to sequence of (a).

16. A method for analyzing a biomolecule in a sample, wherein said method comprising:

(a) altering HYPLIP1 or FCHL1 activity in a sample; and

(b) measuring the concentration of a lipid-associated biomolecule.

19. A method for identifying susceptibility to a lipid disorder which comprises comparing the nucleotide sequence of the suspected FCHL1 allele with a wild-type FCHL1 nucleotide sequence, wherein said difference between the suspected allele and the wild-type sequence identifies a sequence variation of FCHL1 nucleotide sequence.