Genes expressed in mental illness and mood disorders

• US 10,301,615 B2
• Filed: 01/30/2014
• Issued: 05/28/2019
• Est. Priority Date: 03/01/2013
• Status: Active Grant

• Current Assignee: PsychNostics, LLC
• Original Assignee: PsychNostics, LLC
• Inventors: Thiruvengadam, Alagu P., Chandrasekaran, Krish
• Primary Examiner(s): Zhang, Kaijiang
• Application Number:
  US14/763,706
• Publication Number:
  US 20160002623A1
• Time in Patent Office: 1,944 Days
• Field of Search: None
• CPC Class Codes: C12N 15/1034 Isolating an individual clone by screening libraries
• CPC Class Codes: C12Q 1/6806 Preparing nucleic acids for analysis, e.g. for polymerase chain reaction [PCR] assay C12Q1/6804 takes precedence
• CPC Class Codes: C12Q 1/6883 for diseases caused by alterations of genetic material
• CPC Class Codes: C12Q 2600/136 Screening for pharmacological compounds
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: C40B 30/04 by measuring the ability to specifically bind a target molecule, e.g. antibody-antigen binding, receptor-ligand binding
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof

Abstract

The present invention relates to a composition comprising a plurality of cDNA molecules for use in methods of detecting changes in expression of genes encoding proteins that are associated with mental illnesses and which are differentially expressed in patients with mental illnesses, such as bipolar I disorder, bipolar II disorder, unipolar disorder, schizophrenia, attention deficit hyperactive disorders, obsessive compulsive disorders, anxiety disorders or other related mood disorders. The composition and the cDNA molecules may be used in their entirety or in part as to diagnose, to stage, to treat, and/or to monitor the treatment of a subject with mental illness.

Claims

1. A composition comprising a plurality of cDNA molecules, wherein the plurality of cDNA molecules consists of two or more cDNA molecules selected from the group consisting of SEQ ID NOs:

1-50, wherein one or more of SEQ ID NOs;

1-50 may be substituted for by the complement of said cDNA molecule.

2. The composition of claim 1, wherein said plurality of cDNA molecules consists of SEQ ID NOs:

1-8, wherein one or more of SEQ ID NOs;

1-8 may be substituted for by the complement of said cDNA molecule.

4. The composition of claim 1 or 3, wherein the cDNA molecules are immobilized on a substrate.

5. The composition of claim 4, wherein the substrate is selected from the group consisting of a nylon membrane, a nitrocellulose membrane, a polypropylene support, a glass support and a silicon support.

13. A high throughput method of screening a library of molecules or compounds to identify a ligand which specifically binds a cDNA molecule, the method comprising:

(a) combining the composition of claim 1 with the library of molecules or compounds under conditions to allow specific binding; and

(b) detecting specific binding between each cDNA molecule and at least one molecule or compound, thereby identifying a ligand that specifically binds to each cDNA molecule.

14. The method of claim 13 wherein the library is selected from the group consisting of DNA molecules, RNA molecules, mimetics, peptides, peptide nucleic acids, proteins, and transcription factors.

20. A high throughput method for detecting differential expression of two or more cDNA molecules in a sample containing nucleic acids, the method comprising:

(a) combining the composition of claim 1 with nucleic acids of the sample, forming one or more hybridization complexes; and

(b) detecting the hybridization complexes; and

(c) comparing the hybridization complexes with those of a standard, wherein differences in the size and intensity of each hybridization complex indicates differential expression of cDNAs in the sample.

21. The high throughput method of claim 20, wherein the two or more cDNA molecules are differentially expressed in a sample from a subject with a mental illness in comparison with a standard from a subject without a mental illness.

22. The high throughput method of claim 21, wherein said differential expression is a downregulation of at least two-fold in said sample from said subject with a mental illness.

23. The high throughput method of claim 21, wherein the mental illnesses is selected from the group consisting of bipolar I disorder, bipolar II disorder, unipolar disorder, schizophrenia, an attention deficit hyperactive disorder, an obsessive compulsive disorder, an anxiety disorder and a mood related disorder.

3. A composition comprising a plurality of cDNA molecules, wherein the plurality of cDNA molecules consists of SEQ ID NOs:

1-15, wherein one or more of SEQ ID NOs;

1-15 may be substituted for by the complement of said cDNA molecule.

18. A high throughput method of screening a library of molecules or compounds to identify a ligand which specifically binds a cDNA molecule, the method comprising:

(a) combining the composition of claim 3 with the library of molecules or compounds under conditions to allow specific binding; and

(b) detecting specific binding between each cDNA molecule and at least one molecule or compound, thereby identifying a ligand that specifically binds to each cDNA molecule.

19. The method of claim 18 wherein the library is selected from the group consisting of DNA molecules, RNA molecules, mimetics, peptides, peptide nucleic acids, proteins, and transcription factors.

6. An array comprising a plurality of cDNA molecules immobilized on a substrate, wherein the plurality of cDNA molecules consists of two or more cDNA molecules selected from the group consisting of SEQ ID NOs:

1-50, wherein one or more of SEQ ID NOs;

1-50 may be substituted for by the complement of said cDNA molecule.

7. The array of claim 6, wherein said plurality of cDNA molecules consists of SEQ ID NOs:

1-8, wherein one or more of SEQ ID NOs;

1-8 may be substituted for by the complement of said cDNA molecule.

9. The array of claim 6 or 8, wherein the substrate is selected from the group consisting of a nylon membrane, a nitrocellulose membrane, a polypropylene support, a glass support and a silicon support.

10. A high throughput method for detecting differential expression of one or more cDNA molecules in a sample containing nucleic acids, the method comprising:

(a) hybridizing the array of claim 6 with nucleic acids of the sample, thereby forming one or more hybridization complexes;

(b) detecting the hybridization complexes; and

(c) comparing the hybridization complexes with those of a standard, wherein differences in the size and intensity of each hybridization complex indicates differential expression of cDNAs in the sample.

11. The method of claim 10, wherein the sample is blood or is obtained by separation from blood.

12. The method of claim 10 wherein the nucleic acids are amplified prior to hybridization.

8. An array comprising a plurality of cDNA molecules immobilized on a substrate, wherein the plurality of cDNA molecules consists of SEQ ID NOs:

1-15, wherein one or more of SEQ ID NOs;

1-15 may be substituted for by the complement of said cDNA molecule.

15. A high throughput method for detecting differential expression of one or more cDNA molecules in a sample containing nucleic acids, the method comprising:

(a) hybridizing the array of claim 8 with nucleic acids of the sample, thereby forming one or more hybridization complexes;

(b) detecting the hybridization complexes; and

(c) comparing the hybridization complexes with those of a standard, wherein differences in the size and intensity of each hybridization complex indicates differential expression of cDNAs in the sample.

16. The method of claim 15 wherein the nucleic acids are amplified prior to hybridization.

17. The method of claim 15, wherein the sample is blood or is obtained by separation from blood.