Outline

1. INTRODUCTION AND AIMS

1.1. Introduction

1.1.1. A Familial Disease
1.1.2. Different forms of alcoholism

1.2. Twin, Family and Adoption Studies

1.2.1. Twin Studies
1.2.2. Family Studies
1.2.3. Adoption Studies

1.3. Electrophysiological and Biochemical markers of alcoholism

1.3.1. Electrophysiological Markers of Alcoholism
1.3.2. Biochemical Markers

1.4. Linkage studies

1.5. Association studies

1.6. Dopamine and Dopamine Receptors

1.6.1. The Candidate Gene Approach
1.6.2. Dopamine Receptors

1.7. The Dopamine D2 Receptor Gene (DRD2)

1.8. Association of the A1 allele of the DRD2 gene with alcoholism - studies for and against

1.8.1. Association Studies on Other Populations

1.9. Meta-analytical studies

1.10. Population Frequencies of the A1 Allele

1.11. Other Polymorphisms

1.12. Possible Mechanisms

1.13. Aims

2. MATERIALS AND METHODS

2.1. Materials

2.2. Collection of Patients and Controls

2.2.1. Langton Clinic
2.2.2. NSW Red Cross Blood Transfusion Service
2.2.3. Myanmar (Burmese) population, Kayin region

2.3. Extraction of genomic dna from whole blood

2.4. Polymerase Chain Reaction (PCR)

2.5. Gel electrophoresis of PCR products

2.6. TaqI digestion of PCR products

2.7. Polyacrylamide gel electrophoresis of digested DNA

2.8. Genotyping Individuals

2.9. Microsatellite Polymorphism

2.9.1. Primers
2.9.2. Polymerase Chain Reaction
2.9.3. Gel Electrophoresis

2.10. Statistics

2.10.1. Conformity to Hardy-Weinberg Equilibrium
2.10.2. chi-2 testing using r x c contingency tables
2.10.3. Heterogeneity Test

3. RESULTS

3.1. Polymerase Chain Reaction

3.2. Restriction Digests

3.2.1. A1/A2 Genotype

3.3. Statistical Analysis of Results

3.3.1. Hardy-Weinberg Equilibrium
3.3.2. Heterogeneity Testing
3.3.3. Comparison of phenotypes
3.3.4. Comparison of A1 allele prevalence
3.3.5. Comparison of gene counts

3.4. Meta-analytical Studies

3.4.1. Hardy-Weinberg Equilibrium
3.4.2. Heterogeneity Testing
3.4.3. Comparison of studies

3.5. Microsatellite Polymorphism

4. DISCUSSION

4.1. The Current Study

4.2. Possible reasons for a lack of association

4.3. A Meta-analysis

4.4. Possible reasons for a demonstrated association

4.5. Reasons for association but no linkage in families

4.6. The Future

4.6.1. Sampling
4.6.2. Haplotype analysis

4.7. Conclusions

REFERENCES

APPENDICES