# Characterization of Tandem Repeat and Structural Variants Contributing to Addictive Behaviors in Mice and Rats

> **NIH NIH U01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $648,766

## Abstract

PROJECT SUMMARY
 Genome-wide association studies (GWAS) in model organisms such as mice and rats have
identified hundreds of genetic loci that are associated with addictive behaviors, but determining the causal
genes remains challenging. Single nucleotide polymorphisms (SNPs) may not adequately tag other classes
of variants such as structural and repetitive variants that have higher mutation rates. Thus, both panels of
inbred strains and outbred populations will fail to identify a subset of loci and causal alleles. We are
proposing to address this serious limitation by using cutting-edge methods to discover and genotype
structural variants (SVs) and tandem repeats (TRs). Because they are technically challenging to analyze,
SVs and TRs have not yet been adequately surveyed in rodents. However, there is already extensive
evidence that SVs and TRs are prevalent in mice and rats, and that they have important functional
consequences. Our proposal brings together complementary expertise in human genetics and bioinformatic
analysis of SVs (Sebat) and repetitive variation (Gymrek) with established leadership in elucidating the
genetic basis of behavioral phenotypes in model organisms (Palmer). This study will generate the first
large-scale resource for analyzing the effects of complex variation on mouse and rat phenotypes. We use
this resource to examine gene expression and behavioral traits in inbred mice (BXD recombinant inbred
strains, the Hybrid Mouse Diversity Panel (HMDP), the Diversity Outbred (DO) mice, the Hybrid Rat
Diversity Panel (HRDP) and the Heterogeneous Stock (HS) outbred rats.
 In Specific Aim 1 we will characterize SVs in inbred and outbred mice and rats by single-molecule
sequencing. In Specific Aim 2 we will genotype TR in inbred and outbred mice and rats. Finally, in
Specific Aim 3 we will perform GWAS using SV and TR for gene expression and behavioral traits. We will
determine the phenotypic consequences of the SV and TR genotypes on gene expression and behavioral
traits. We will impute SVs and TRs into outbred mice and rats and then perform GWAS using the wealth of
preexisting gene expression and behavioral data that are available for the mouse and rat populations
studied in this project. Completion of this project will characterize the SV and TR landscape in mice and
rats, elucidate their role in gene expression and complex behavioral traits relevant to addiction, and create
a community resource that will enhance numerous ongoing mouse and rat genetic studies.

## Key facts

- **NIH application ID:** 10818588
- **Project number:** 5U01DA051234-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Melissa Gymrek
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $648,766
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10818588

## Citation

> US National Institutes of Health, RePORTER application 10818588, Characterization of Tandem Repeat and Structural Variants Contributing to Addictive Behaviors in Mice and Rats (5U01DA051234-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10818588. Licensed CC0.

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