Dysfunction of the dopaminergic system has been implicated in a variety of neurological disorders including schizophrenia, bipolar disorder and drug addiction. The dopamine transporter protein is a key regulator of dopaminergic homeostasis. Our long-term objective is to identify susceptibility genes involved in dopamine-regulated disorders. With this aim in mind, we performed a mouse forward mutagenesis screen to identify genetic interactions with the dopamine transporter. We have mapped a putative enhancer and suppressor of the dopamine transporter to chromosomes 18 and 16, respectively. In this proposal, we will employ whole exome sequencing to identify the causative mutations underlying these previously mapped loci. Identification of these modifiers will lead to a better understanding of dopamine regulation and may lead to novel treatments for a variety of neurological disorders.
Aberrant dopamine regulation is implicated in a variety of neurological disorders, including schizophrenia, bipolar depression, Parkinson's, and drug addiction. We propose to use next generation sequencing to identify genes that regulate dopamine levels in the brain. Our findings will help us better understand dopamine regulation and may provide new leads on treatments for a variety of neurological disorders.
| Speca, David J; Trimmer, James S; Peterson, Andrew S et al. (2017) Whole exome sequencing reveals a functional mutation in the GAIN domain of the Bai2 receptor underlying a forward mutagenesis hyperactivity QTL. Mamm Genome 28:465-475 |
