# Genetic and functional assessment of human-specific duplicated genes

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $38,215

## Abstract

PROJECT SUMMARY
Recent advances in sequencing technologies and bioinformatics have created an emerging picture of
structurally dynamic human and non-human primate genomes. In addition to single-nucleotide variants, larger
structural variants (SVs; e.g., deletions, duplications, and inversions) are prolific within and between species
but are more difficult to study. SVs are often too large to reliably identify with short-read (e.g., Illumina) data
and frequently coincide with repetitive elements, making these loci historically difficult to assemble, annotate,
and functionally investigate. Despite this, SV-associated rearrangements are known to cause morphological
and neurodevelopmental abnormalities in humans, and a handful of human-specific duplicated (HSD) genes
have been linked to innovative neurological features. The potential functional impact of SVs is enormous, as
single mutational events can rearrange genes and regulatory elements throughout the genome. However,
while the genes themselves have received growing attention, the regulatory landscape of SVs remains poorly
characterized. Gene expression differences are known to contribute to a variety of human diseases, and are
thought to be a major contributor to phenotypic divergence between species. SVs thus represent an
understudied and likely impactful set of loci to examine in this light. This is particularly intriguing in the case of
HSD genes, which show distinct expression patterns despite having nearly identical sequences. This work will
use genomic techniques to investigate the effect of evolutionarily recent SVs on gene expression between
humans and chimpanzees. This will be accomplished via three approaches: (1) high-throughput assay of
human-duplicated regulatory element activity; (2) identification of differences in the promoter-enhancer
connectome across SV breakpoints; and (3) testing for causal relationships between candidate regulatory
features and gene expression at SV loci of functional significance. The findings of this research will be the first
to characterize hundreds of loci in parallel and will offer insight into the mechanistic basis for regulatory
changes between primate species.

## Key facts

- **NIH application ID:** 10156595
- **Project number:** 1F31HG011205-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Colin James Shew
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,215
- **Award type:** 1
- **Project period:** 2021-01-12 → 2023-01-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156595

## Citation

> US National Institutes of Health, RePORTER application 10156595, Genetic and functional assessment of human-specific duplicated genes (1F31HG011205-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10156595. Licensed CC0.

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