# Understanding genetic risk for aneuploid conception

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2024 · $503,222

## Abstract

Project Summary/Abstract
Because infertility is a growing public health problem, it is imperative that we understand the
basic mechanisms and identify the genetic risk factors that give rise to this disease. The most
common genetic abnormality that causes miscarriage is aneuploidy, an embryo with an improper
number of chromosomes. Although increased risk of aneuploidy is strongly correlated with
increasing maternal age, significant variation exists in aneuploidy rates at any given age, making
age alone an inadequate biomarker for the risk of producing an aneuploid conception. Therefore,
we hypothesize that women who produce higher than average levels of preimplantation stage
aneuploidy at a given age possess causal variants in genes which predispose them to an early
risk of producing an aneuploid conception. To test this hypothesis, we will develop methods to
identify causal genes using low-coverage whole genome sequences obtained from blastocysts
that underwent preimplantation genetic testing for aneuploidy (PGT-A). PGT-A sequencing is
common for clinical care to guide single euploid embryo transfer, and therefore there is an
abundance of sequences to analyze. Success in method development will likely have far reaching
utility in enabling clinics to conduct their own genetics-based evaluations. Candidate genes
identified by PGT-A analysis in this project and from previously analyzed datasets will be rapidly
tested and validated for causation by using worm and fly model organisms. High-ranking
candidates, and candidates without model organism homologs, will undergo one final validation
pass in a mouse oocyte in vitro system, before creating mouse models that harbor the genetic
variant of interest for in vivo studies that are not possible to conduct in humans. These
approaches will shed light on the molecular mechanisms that control meiotic chromosome
segregation in female gametes. Ultimately, this study could lead to the identification of maternal
genetic markers for risk of producing an aneuploid conception and help avoid infertility by
empowering women with necessary and personalized information to better preserve their
individual fertility.

## Key facts

- **NIH application ID:** 10884180
- **Project number:** 5R01HD091331-07
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** Karen A Schindler
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $503,222
- **Award type:** 5
- **Project period:** 2017-12-15 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10884180

## Citation

> US National Institutes of Health, RePORTER application 10884180, Understanding genetic risk for aneuploid conception (5R01HD091331-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10884180. Licensed CC0.

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