# Structural and functional consequences of disease SNP's on the transcriptome

> **NIH NIH R01** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $322,350

## Abstract

SUMMARY
Genetic association studies identify the genotypes that correlate with specific phenotypes. A significant portion
of the Single Nucleotide Polymorphisms (SNPs) that associate with human disease phenotypes map outside of
the protein coding regions of genes. In these cases, the precise molecular mechanism of the disease etiology
is not immediately apparent. This proposal focuses specifically on SNPs that map to non-coding and
UnTranslated Regions (UTRs) of genes. If these SNPs alter the structure of the RNA, they are classified as a
riboSNitch. We will experimentally validate eight novel, computationally predicted riboSNitches associated with
the human diseases amyotrophic lateral sclerosis, breast and colorectal cancer, dyskeratosis, Hirschsprung's
disease, lipase deficiency, microcephalic dwarfism, and schizophrenia. Our work will leverage significant
advances in the throughput and accuracy of chemical structure probing techniques in combination with next
generation sequencing. Furthermore, these techniques now enable us to probe RNA structure in vivo allowing
us to further understand how the cellular environment affects RNA folding and the function of riboSNitches. We
will also perform quantitative luciferase reporter assays and leverage Tet-off inducible systems to study the
functional consequences of validated riboSNitches on translation and RNA stability to establish disease
causality. Together, our findings will establish SNP-induced RNA structure change in multiple new human
diseases and broaden understanding of RNA structure in shaping human phenotype.

## Key facts

- **NIH application ID:** 10017258
- **Project number:** 5R01GM101237-08
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Alain T Laederach
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $322,350
- **Award type:** 5
- **Project period:** 2012-05-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10017258

## Citation

> US National Institutes of Health, RePORTER application 10017258, Structural and functional consequences of disease SNP's on the transcriptome (5R01GM101237-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10017258. Licensed CC0.

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