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Identification of causal DNA variants that influence gene expression in trans

Award Number: F31HG015201
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/28/2026
PERIOD OF PERFORMANCE END DATE: 09/27/2028

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Identification of causal DNA variants that influence gene expression in trans - PROJECT SUMMARY Genetic variation underlies much of the phenotypic variation in important traits, including morphological and physiological phenotypes as well as risk for common diseases, among individuals. Population-scale genome- wide association studies (GWAS) have identified thousands of genetic loci containing variants associated with a variety of complex traits and diseases, but knowledge of variant associations alone does not inform how variants influence these traits. Complementing GWAS is expression quantitative trait loci (eQTL) mapping, which accounts for the transcriptomic effects of DNA variants. This may explain the mechanisms through which trait-associated variants affect phenotype. Given the importance of such information, it is critical to understand variant effects on gene expression. Most of the variation in gene expression is attributed to trans-acting eQTLs, which are difficult to detect due to their smaller effect sizes relative to cis-eQTLs and the need to overcome multiple testing burden in genome-wide scans. Due to these barriers with studying trans-acting variation in humans, we do not know the answers to critical questions about the molecular basis of trans-acting regulatory variation. To address this, the yeast Saccharomyces cerevisiae is an ideal model to study trans-acting regulation on phenotypic variation. Previous research in the Albert lab applied the power of yeast as a generalizable model for human genetics has shown that most trans-eQTLs cluster in hotspots across the genome. These hotspots have an outsized, genome-wide effect on transcript abundance, yet most of the causal variants for these loci are unknown. In two complementary aims, I will (Aim 1) dissect and deeply profile a carefully selected set of candidate variants that may affect gene expression in trans in a range of environments, and (Aim 2) identify and study trans-acting causal variants at genome-wide scale. Genome engineering, RNA-seq, and bioinformatic analyses will be employed. The central hypothesis is that DNA variants that cause trans-eQTL hotspots affect gene expression and cellular growth by altering proteins involved in different biochemical pathways. This proposal leverages yeast trans-eQTL hotspots as an ideal, tractable model with broad relevance for eukaryotic life. Collectively, the impact of the proposed work will be to broaden understanding of the effects of natural genomic variation on phenotype. In addition to the research proposal, the other components of the fellowship application include a comprehensive and rigorous set of research and clinical training plans that will support the successful completion of my MD and PhD degrees and will foster my development into a physician scientist who works to pinpoint causal genes and variants that underlie different conditions and explore the mechanisms through which they affect human health.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $50,114 )
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Human Genome Research	001	1	9/23/2026	NEW	$0
2026	2026	REGENTS OF THE UNIVERSITY OF MINNESOTA	2221 UNIVERSITY AVE SE STE 100	MINNEAPOLIS	MN	55414	HENNEPIN	USA	Human Genome Research	000	1	9/23/2026	NEW	$50,114
														Subtotal = $50,114

Grand Total All Awards = $50,114

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Identification of causal DNA variants that influence gene expression in trans

Award Number: F31HG015201

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/28/2026

PERIOD OF PERFORMANCE END DATE: 09/27/2028

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