Allelic association of the human dopamine(D2) receptor gene in compulsive disorders

• US 5,500,343 A
• Filed: 06/24/1992
• Issued: 03/19/1996
• Est. Priority Date: 02/07/1990
• Status: Expired due to Term

• Current Assignee: Regents of the University of California (University of California), Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Regents of the University of California (University of California), Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Sheridan, P. J., Noble, E. P., Blum, Kenneth
• Primary Examiner(s): Jones, W. Gary
• Assistant Examiner(s): Sisson, Bradley L.
• Application Number:
  US07/909,383
• Time in Patent Office: 1,364 Days
• Field of Search: 435/6, 435/91, 435/975, 435/91.1, 435/91.2, 435/810, 536/23.1, 536/23.5, 536/24.31, 536/24.33, 935/78, 935/31
• US Class Current: 435/6.16
• CPC Class Codes: C12Q 1/6876 Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• 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: C12Q 2600/172 Haplotypes
• CPC Class Codes: Y10S 435/81 Packaged device or kit

Abstract

In an important embodiment, the present invention concerns a method for detecting compulsive disorder susceptibility of a human. The method comprises initially obtaining a DNA sample of said human and then determining the presence or absence of a particular human D₂ receptor gene allele in said sample. Detection of said allele in the sample is indicative of susceptibility to compulsive disorder. A most preferred embodiment is to detect a susceptibility to alcoholism and cocaine dependence, particularly because said allele has been found to be present in a majority of clinically diagnosed alcoholics and cocaine users. The human D₂ receptor gene A1 and B1 alleles are most preferably detected in said sample.

Claims

1. A method of detecting a genetic potential susceptibility to cocaine dependence in a human subject, comprising:

isolating DNA from said subject; and

detecting, in said DNA, a human dopamine D₂ receptor gene A1 or B1 allele indicating

a potential susceptibility to cocaine dependence.

3. The method of claim 1 wherein the detecting involves RFLP.

4. The method of claim 1 wherein the detecting involves PASA.

5. The method of claim 1 wherein the human dopamine D2 receptor gene allele is an A1 allele.

6. The method of claim 1 wherein the human dopamine D2 receptor gene allele is a B1 allele.

2. A method of detecting a genetic potential susceptibility to alcoholism or cocaine dependence in a human subject, comprising:

obtaining DNA from said subject;

subjecting said DNA to digestion by TaqI restriction enzyme; and

detecting, in said DNA, a human dopamine D₂ receptor gene A1 or B1 allele indicating a potential susceptibility to alcoholism or cocaine dependence by hybridizing said DNA to a labeled A1- or B1-specific probe.

7. A method of detecting a genetic potential susceptibility to cocaine dependence in a human subject, comprising:

obtaining DNA from said subject;

subjecting said DNA to digestion by TaqI restriction enzyme;

hybridizing said DNA to a labeled probe specifically binding the A1 allele of the human dopamine D₂ receptor; and

detecting in said DNA an A1 allele.

8. A method for detection of a genetic potential susceptibility to cocaine dependence in a human subject, comprising:

obtaining DNA from said subject;

subjecting said DNA to digestion by TaqI restriction enzyme;

hybridizing said DNA to a labeled probe specifically binding the B1 allele of the human dopamine D₂ receptor; and

detecting in said DNA a B1 allele.

9. A kit for use in genetically detecting potential susceptibility to alcoholism or cocaine dependence in a human subject, said kit comprising:

(a) a carrier compartmentalized to receive one or more container means in close confinement therein;

(b) a first container means including a TaqI restriction enzyme capable of cleaving a human dopamine D₂ receptor gene; and

(c) a second container means including a hybridization probe for detecting a human dopamine D₂ receptor gene A1 or B1 allele whose presence indicates a potential genetic susceptibility to alcoholism or cocaine dependence, said hybridization probe specifically binding either the 6.6-kb TaqI fragment comprising said A1 allele or the 4.6-kb TaqI fragment comprising said B1 allele.

10. A method for the detection of genetic potential susceptibility to alcoholism in a human subject comprising:

isolating a DNA sample from the subject;

performing PCR amplification of specific alleles using primer #3208 or primer #3420;

separating amplification products; and

detecting the presence or absence of an approximately 241 bp band, said band indicating the presence of the human dopamine D₂ receptor gene allele DRD2^In6-Ex7 haplotype I allele which is indicative of a potential genetic susceptibility to alcoholism.