Genetic Basis of Opioid Dependence Vulnerablility
The goal of this project is to exploit an outbred animal model of opioid abuse research, coupled with comprehensive genomic characterization, to improve detection of the underlying phenotypic and genomic changes associated with transition to opioid abuse. In Aim 1, we will exploit a validated outbred animal model of heroin self- administration with extended access that produces behavioral phenotypes consistent with increased drug consumption, accelerated motivation for drug intake and elevated drug-seeking in periods of drug absence. Aim 2, we will carry out a genome-wide association study (GWAS) using genotyping by sequencing (GBS) on 1,000 animals sampled from the two locations. In Aim 3, we will assess the genomic impact of the genetic variants uncovered in Aim 2 via high throughput RNA sequencing to assess gene expression of relevant functional genes and uncover expression quantitative trait loci (eQTLs). Chromosome conformation capture (3C) will be used to physically link an eQTL with its target gene assigning causality to a variant and its regulated gene.
Methods for genotype
Low-coverage WGS based on Riptide library preparation (pulication in progress)
Methods for Phenotypes
Self AdministrationHeroin self- administration with extended access that produces behavioral phenotypes consistent with increased drug consumption, accelerated motivation for drug intake and elevated drug-seeking in periods of drug absence.cocaine conditioned cue preference
Methods for Omics