# Cancer, speciation, and chromosomes: how somatic chromosome pairing influences gene expression

> **NIH NIH F32** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $65,310

## Abstract

Project Summary
 Homologous chromosome pairing, the physical matching up of homologous chromosomes, is a
fundamental aspect of chromosome mechanics. In most organisms, pairing must occur only during meiosis to
allow for recombination. Accidental pairing at other times can lead to numerous problems, including aneuploidy
and many types of cancer. Understanding the mechanisms that control such somatic pairing will provide insight
into fundamental aspects of chromosome biology.
 To study homologous chromosome pairing in somatic cells, we require a system where we can perform
controlled manipulations of the state of pairing across the genome. Unlike most other organisms, Drosophila
flies pair all of their somatic chromosomes all of the time; however, the offspring of one Drosophila
melanogaster fly and one Drosophila simulans fly lose pairing in a small number of replicable regions of the
genome. This phenomenon is an opening that we can exploit to understand somatic pairing broadly.
Drosophila's wealth of genetic tools, presence of somatic pairing in normal flies, and aberrant pairing in hybrid
flies provide a powerful system to understand the mechanistic basis of pairing.
 I plan to measure pairing in normal individuals and interspecies hybrids by using the Hi-C sequencing
technique. This approach will provide the first genome-wide description of properly and aberrantly paired
genome regions in interspecies hybrids. I will then use the D. melanogaster genome annotation to identify
genome features such as genes and repeated DNA motifs that are overrepresented in non-pairing regions.
DNA features that are consistently found where pairing is lost will provide insight into the factors that govern
pairing. I will confirm these features by up- or down-regulating pairing-related genes, changing the rate of
pairing across the chromosomes and replicating the results of the interspecies hybridization. Because pairing
is known to influence gene expression through the phenomenon of transvection, I will use allele-specific
expression to measure each gene's cis- and trans- regulation with and without pairing, demonstrating the effect
of pairing on gene expression. Together, these experiments will characterize the mechanisms that underlie the
fundamental process of chromosome pairing. This new knowledge will inform our understanding of pairing as it
relates to cell function, disease, and evolution.

## Key facts

- **NIH application ID:** 9840392
- **Project number:** 5F32GM129931-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** James Guy Baldwin-Brown
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $65,310
- **Award type:** 5
- **Project period:** 2019-03-13 → 2021-07-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9840392

## Citation

> US National Institutes of Health, RePORTER application 9840392, Cancer, speciation, and chromosomes: how somatic chromosome pairing influences gene expression (5F32GM129931-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9840392. Licensed CC0.

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