# Species-wide survey of the phenotypic impact of genomic structural variation in yeast

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2022 · $270,831

## Abstract

ABSTRACT
Elucidating the underlying genetic causes of the awesome phenotypic diversity observed in natural
populations is a major challenge in biology. Despite the importance of understanding the genetic basis of
complex traits, we currently lack complete knowledge of the relevant genetic components. Genetic variation
affecting the structure and copy number of chromosomal segments is an underappreciated component of the
genetic architecture. In this proposal, we seek to obtain a species-wide view of structural variation (SV) and
copy number variation (CNV) and how these contribute to the phenotypic landscape of natural populations. In
order to accomplish this, we will take advantage of the genetic workhorse Saccharomyces cerevisiae, for which
we have recently completed whole genome resequencing of 1,011 natural isolates, plus accompanying large
scale phenotyping efforts. CNVs are frequent in our strain collection and have outsize phenotypic affects in the
association tests we have so far completed. We propose to: Aim 1. Apply long read sequencing to better
characterize the structural variation present in these strains and generate high quality de novo assemblies. In
Aim 2, we will collect quantitative strain phenotypes over a large panel of environmental conditions, with a
particular emphasis on conditions that we and others have found to be particularly sensitive to CNVs. We will
also include molecular traits such as mRNA and protein abundance. We will then perform association testing
with the variants discovered in Aim 1 in order to determine over an entire species the degree to which SVs and
CNVs contribute to trait variation. Since association methods perform poorly for rare genetic variants, we will
in Aim 3 use a diallel panel where controlled crosses allow us to better survey all variation present. Finally, in
Aim 4 we will complement our work on naturally occurring variation by building libraries of engineered
variants. We will create large dosage series pools of segmental amplifications and deletions to better
understand their consequences across multiple genetic backgrounds. Our work will result in a more complete
understanding of the complexities of the genotype-phenotype connection with respect to this important but
understudied class of genetic variants.

## Key facts

- **NIH application ID:** 10499194
- **Project number:** 1R01GM147040-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Maitreya J Dunham
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $270,831
- **Award type:** 1
- **Project period:** 2022-09-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499194

## Citation

> US National Institutes of Health, RePORTER application 10499194, Species-wide survey of the phenotypic impact of genomic structural variation in yeast (1R01GM147040-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499194. Licensed CC0.

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