# Expanding the utility of prenatal genetic testing

> **NIH NIH F30** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $38,093

## Abstract

PROJECT SUMMARY
Congenital abnormalities affect 3-4% of pregnancies and cause 20-30% of neonatal deaths worldwide. Prenatal
diagnosis can lead to significant improvements in newborn health and development for a growing number of
genetic conditions, especially as treatment options, such as gene therapy, continue to increase. Non-invasive
prenatal testing (NIPT) is now widely available for chromosomal abnormalities, and more recently, for identifying
paternally-inherited/de novo autosomal dominant conditions in the fetus. Additionally, more and more women
are being offered whole-exome sequencing (WES) on amniocentesis or chorionic villus samples after structural
abnormalities in the fetus are identified on ultrasound. However, current WES paradigms lack the power to detect
exon-level CNV and NIPT options for recessive single-gene disorders do not exist.
Recessive conditions constitute over half of single-gene disorders, and the vast majority of known single-gene
conditions are caused by single-nucleotide polymorphisms (SNPs). While large-scale sequencing efforts are
better defining the prevalence of SNPs, the genome-wide prevalence of exon-level copy number variation (CNV)
remains largely unknown. Research on a limited number of genes would suggest small CNVs represent roughly
1% of variants, but over 9% of pathogenic variants.
We are collecting two cohorts of clinical samples: (1) mother-father-fetus trios when structural abnormalities are
found on ultrasound; (2) maternal blood during pregnancy and cord blood at time of delivery. Using these clinical
samples, the Specific Aims of this proposal are: (1) Demonstrate multiplexed exome capture utility and novel
analysis for exon-level CNV detection and (2) Develop analysis framework and novel probes for fetal genotyping
from maternal cell-free DNA. Aim 1 will employ the CNV algorithm (mcCNV) in trios to identify exon-level de novo
variation, increasing the diagnostic yield and ideally identifying new candidate genes for understanding human
development. Aim 2 greatly expands the possible utility of NIPT with the novel inclusion of recessive single-gene
disorders.
Through this research proposal and associated training plan, I will gain a unique and interdisciplinary skill-set that
combines data science and biostatistics with population genetics in an innovative manner that is at the forefront
of maternal-fetal medicine. This training will provide me with the technical, statistical, and professional skills I
need to become a leader at an academic center and to pursue my goals of practicing maternal-fetal medicine
and research as a physician-scientist.

## Key facts

- **NIH application ID:** 10025575
- **Project number:** 5F30HD101228-02
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Dayne Lewis Filer
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,093
- **Award type:** 5
- **Project period:** 2019-11-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10025575

## Citation

> US National Institutes of Health, RePORTER application 10025575, Expanding the utility of prenatal genetic testing (5F30HD101228-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10025575. Licensed CC0.

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