# Investigating the role of structural variation in hominin evolution.

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2022 · $46,752

## Abstract

PROJECT SUMMARY
Along with differences in the environment, genetic variation is the ultimate source of phenotypic diversity within
and between species. Due to the limitations of traditional short-read sequencing technologies, most research in
human genetics and evolution has focused on single-nucleotide variants (SNVs) and short insertions and
deletions. The recent development of long-read sequencing technologies has begun to reveal the prevalence
and phenotypic impacts of larger insertions, deletions, and rearrangements, collectively termed structural
variants (SVs). However, long-read sequencing methods remain impractical for large-scale application due to
their high cost and low throughput. Consequently, the role of SVs in human evolution is still poorly understood.
 These challenges motivate the development of innovative computational approaches that combine the
accuracy of SV discovery using long reads with the scale and global diversity of short-read sequencing
datasets. To advance knowledge of how SVs impact fitness and genome function in humans, this proposed
research project will:
 1. Identify locally adaptive SVs by leveraging graph-based methods for SV genotyping. This approach
 enables accurate genotyping of SVs discovered with long reads in short-read datasets from diverse
 human populations. The population-wide genotypes generated with this method will allow for the
 discovery of signatures of historical positive selection on SVs.
 2. Discover SVs that are shared among or exclusive to the modern human, Neanderthal, and
 Denisovan lineages using both graph genotyping and alignment-free methods. Placing SVs in their
 comparative evolutionary contexts will reveal divergent variants that may underlie important functional
 differences that distinguished these hominin groups.
 3. Quantify the functional genomic impacts of SVs by combining long-read and short-read RNA
 sequencing of diverse human individuals. This data will reveal insights into how SVs may mediate
 phenotypic differences through effects on gene expression and splicing.
This research will be conducted in a strong genetics and genomics training environment, and will combine the
evolution, computational genomics, and long-read sequencing expertise and resources of my sponsor, co-
sponsor, and collaborator. My project will provide me with scientific training in evolutionary modeling,
development of software tools, and functional genomic data analysis. Meanwhile, the institutional environment
will also facilitate my training in the communication, teaching, mentorship, and leadership skills that are
essential for becoming a leading researcher in human genetics.

## Key facts

- **NIH application ID:** 10464600
- **Project number:** 1F31HG012495-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Stephanie M Yan
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $46,752
- **Award type:** 1
- **Project period:** 2022-09-16 → 2024-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10464600

## Citation

> US National Institutes of Health, RePORTER application 10464600, Investigating the role of structural variation in hominin evolution. (1F31HG012495-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10464600. Licensed CC0.

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