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Study Of Tyrosine Hydroxylase (Th) Gene Sequence Variations In Association With Δ9-Tetrahydrocannabinol (Thc) Dependence

By: Ali Raza (2015-VA-446) | Dr. Maryam Javed.
Contributor(s): Dr. Asif Nadeem | Prof. Dr. Tahir Yaqub.
Material type: materialTypeLabelBookPublisher: 2017Description: 75P.Subject(s): Forensic ScienceDDC classification: 2858-T Dissertation note: Anti-Social Personality Disorder (ASPD) is ability of an individual to adopt social norms. These ASPDs are driving force in majority of criminal activities. Dopamine being important neurotranmiter of nervous system controls major behavioral traits. Low level of dopamine can be causative factor for an individual to start drug abuse to restore it because majority of drug are proven to enhance dopamine production. In this study genetic exploration of genes coding for dopamine producing enzymes. Tyrosine Hydroxylase (TH) gene was selected and its two regions (Intron 1 and exon 3) were amplified and analyzed through Sanger’s sequencing method followed by statistical analysis. Total five SNP were recorded at locus TH1, TH2, TH3, TH4, and TH5. One insertion, three transversion and only one mutation was transition. No exonic mutation was recorded hence no change in protein structure was found. Mutations at TH1 and TH4 were found to be highly associated with addiction. Mutant “B” allele were also present but still wild “A” was most common allele in our population. TH1, TH2, TH4 have positive correlation with addiction, TH3 is correlated with Nicotine and TH5 shown protective role against nicotine. There are few genetic changes in our population that can be associated with drug addiction statistically but still there prevalence in our gene pool is very low. We can conclude on the basis of these findings that drug addiction in our population is more likely a social issue rather than genetical. Limitations of our research was sample size. There are further possibilities for this project to investigate on mRNA level. Advanced neurobiological techniques can also be applied on subjects to analyze dopamine level in different brain regions. For genetic studies epistatic role of few other genes can also be considered for validation.
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Veterinary Science 2858-T (Browse shelf) Available 2858-T
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Anti-Social Personality Disorder (ASPD) is ability of an individual to adopt social norms. These ASPDs are driving force in majority of criminal activities. Dopamine being important neurotranmiter of nervous system controls major behavioral traits. Low level of dopamine can be causative factor for an individual to start drug abuse to restore it because majority of drug are proven to enhance dopamine production. In this study genetic exploration of genes coding for dopamine producing enzymes. Tyrosine Hydroxylase (TH) gene was selected and its two regions (Intron 1 and exon 3) were amplified and analyzed through Sanger’s sequencing method followed by statistical analysis.
Total five SNP were recorded at locus TH1, TH2, TH3, TH4, and TH5. One insertion, three transversion and only one mutation was transition. No exonic mutation was recorded hence no change in protein structure was found. Mutations at TH1 and TH4 were found to be highly associated with addiction. Mutant “B” allele were also present but still wild “A” was most common allele in our population. TH1, TH2, TH4 have positive correlation with addiction, TH3 is correlated with Nicotine and TH5 shown protective role against nicotine. There are few genetic changes in our population that can be associated with drug addiction statistically but still there prevalence in our gene pool is very low. We can conclude on the basis of these findings that drug addiction in our population is more likely a social issue rather than genetical.
Limitations of our research was sample size. There are further possibilities for this project to investigate on mRNA level. Advanced neurobiological techniques can also be applied on subjects to analyze dopamine level in different brain regions. For genetic studies epistatic role of few other genes can also be considered for validation.

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