# A new system for modeling supernumerary chromosome dynamics and formation during meiosis.

> **NIH NIH K99** · STOWERS INSTITUTE FOR MEDICAL RESEARCH · 2020 · $104,205

## Abstract

PROJECT SUMMARY
The normal growth, development, and reproduction of an organism relies on a defined set of essential
chromosomes. At conception, the gain or loss of whole chromosomes is generally lethal and is thought to be
the leading cause of spontaneous abortions in humans. Though the presence of a whole chromosome can be
lethal, the gain of only part of a chromosome can be viable. Small supernumerary marker chromosomes
(sSMCs) are structurally abnormal chromosomes that are present in ~1/2300 births and have been linked to
infertility, fetal loss, and intellectual and developmental disabilities. Despite their clear impact on human
health, very little is understood about important aspects of sSMC biology. Patient studies and human cell lines
have been instrumental in determining the composition and frequency of existing sSMCs, but these systems
are unable to model sSMC dynamics and formation during complex developmental processes. To close this
knowledge gap, I will use the supernumerary B chromosomes recently found in D. melanogaster as a tractable
model system to gain fundamental insight into supernumerary chromosome biology during female meiosis.
Similar to some sSMCs described in humans, the B chromosomes can disrupt meiotic chromosome
segregation, are subject to sex-specific differences in transmission frequency to progeny, and were formed
from an essential chromosome. I will determine how B chromosomes disrupt the segregation of essential
chromosomes during female meiosis using a genetic approach to monitor chromosome missegregation relative
to a wide-ranging number of B chromosomes. I will then complement this genetic analysis with the
visualization of live female meioses to gain a comprehensive view of meiotic supernumerary chromosome
dynamics. To elucidate how B chromosomes are preferentially transmitted during female meiosis, I will identify
differences in the centromeres of the B chromosomes and the essential chromosomes with high resolution by
measuring the centromeric domains on chromatin fibers and conducting long-read sequencing and assembly
of centromeric regions. Finally, I will determine the mechanism of supernumerary chromosome formation by
strategically marking one of the essential chromosomes so that I can easily identify the formation of a new
supernumerary chromosome. Based on the unique arrangement of markers this new supernumerary
chromosome carries, I will deduce the mechanism by which it formed. Together, this work will allow me to gain
research training in several areas that are essential for the continued investigation of supernumerary
chromosome dynamics and formation, providing a foundation for my future research as an independent
investigator examining how supernumerary chromosomes promote infertility, reduce gamete quality, and form
de novo during meiosis.

## Key facts

- **NIH application ID:** 10000194
- **Project number:** 5K99HD099276-02
- **Recipient organization:** STOWERS INSTITUTE FOR MEDICAL RESEARCH
- **Principal Investigator:** STACEY L HANLON
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $104,205
- **Award type:** 5
- **Project period:** 2019-08-21 → 2020-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000194

## Citation

> US National Institutes of Health, RePORTER application 10000194, A new system for modeling supernumerary chromosome dynamics and formation during meiosis. (5K99HD099276-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10000194. Licensed CC0.

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