Date of Completion

12-16-2016

Embargo Period

12-16-2016

Keywords

iPSCs, alcoholism, epigenetics, SNPs, DNA CpG methylation

Major Advisor

Dr. Jonathan Covault

Associate Advisor

Dr. Richard Mains

Associate Advisor

Dr. Stormy Chamberlain

Associate Advisor

Dr. Justin Cotney

Field of Study

Biomedical Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Alcohol use disorders (AUDs) affect approximately 13.9% of the population in the United States. Many groups have found a correlation between AUDs and a synonymous SNP in exon 5 of the GABRA2 gene (rs279858 T to C; C allele associated with AUDs). However, the biological effects of this and other SNPs in this region are unknown.

Our lab has been using iPSC technology for the past few years to study AUDs. The lab has shown, using qPCR of mRNA, that a cluster of GABAA receptor subunit genes on chromosome 4p12 is expressed at minimal levels in neural cells derived from half of the iPSC lines studied and expression had a high correlation to genotype. However, subunits for GABAA receptor subunit genes located on other chromosomes showed robust expression in all lines.

Results generated in this thesis project from chromatin immunoprecipitation and DNA CpG methylation experiments suggest that genetic factors linked to the rs279858 tag-SNP may moderate the developmental expression of the chromosome 4p12 GABAA receptor subunit gene cluster by altering epigenetic marks in the promoters of these genes.

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