Clarissa Parker Publishes Groundbreaking Genetics Study

MIDDLEBURY, Vt. – Clarissa Parker, assistant professor of psychology and neuroscience, coauthored a study published in the July 4 edition of the journal Nature Genetics. Parker was first author of the study, which discovered through new methods that two novel genes in mice were associated with methamphetamine sensitivity and anxiety-like behavior.

Parker says in the last decade, findings from genome-wide association studies (GWAS) have led to the conclusion that common DNA sequence and structural differences among people influence their genetic susceptibility to virtually all common diseases. Those studies also face a number of challenges, namely a lack of control over environmental conditions and a need for tens of thousands of research subjects.

Research on mice has addressed some of those challenges, but has traditionally relied on inbred mouse strains, which don’t typically produce information about single genes. Parker’s study changed the traditional method, using 1,200 outbred mice, which are more similar to a natural human population.

According to a University of California at San Diego news story, the new method “takes advantage of the superior mixing that is present in an outbred population to help drill down to specific genes using two steps: genotype-by-sequencing, which sequences about one percent of the mouse genome; and RNA sequencing, which identifies only genes turned ‘on’ in a particular tissue, such as the brain.”

The study found that the mouse gene Azi2 was associated with sensitivity to methamphetamine, and Zmynd11 was associated with anxiety-like behavior.

“Neither of these genes have been previously implicated in these traits,” said Parker. “This may lead to new pharmacological treatments for substance use disorders and anxiety disorders.”

The methods used in this project are generally applicable to any quantitative trait, says Parker, and can vastly accelerate the process of gene identification. “My students and I are currently using this same approach in the newly developed diversity outbred mouse population to identify genes associated with ethanol sensitivity – a risk factor for alcohol use disorders – and conditioned fear – a trait associated with PTSD.”

The study, “Genome-wide association study of behavioral, physiological and gene expression traits in outbred CFW mice,” published July 4, 2016, is available online in the journal Nature Genetics.

This research was funded, in part, by the National Institutes of Health (grants R01GM097737, T32DA07255, T32GM07197, R01AR056280, R01AR060234), Human Frontiers Science Program, and Howard Hughes Medical Institute.

With reporting by Stephen Diehl