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Non-invasive fetal HLA and KIR genotyping of cell-free DNA from maternal blood

Award Number: R21HD118554
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Non-invasive fetal HLA and KIR genotyping of cell-free DNA from maternal blood - ABSTRACT Hypertensive disorders in gestational stages, particularly preeclampsia, are a leading cause of maternal mortality globally, accounting for approximately 14% of maternal deaths and affecting 62,000 to 77,000 women annually. In the US, Afican American mothers face a 60% higher prevalence and a threefold higher mortality rate compared to others. This study focuses on the immune-related gene families KIR (killer-cell immunoglobulin-like receptor) and HLA (human leukocyte antigen), whose maternal-fetal genotype interactions significantly influence preeclampsia risk. A specific KIR-HLA combination increases preeclampsia risk twofold, but the clinical application has been limited by technical challenges in fetal genotyping. Our project aims to develop a non-invasive test for early gestational risk stratification of preeclampsia using cell-free fetal DNA (cfDNA) from maternal blood. This proposal aligns with the White House Executive Order to Advance Research and the Notice of Special Interest for High Priority Areas in Placental Research. Our team will develop a high-resolution HLA genotyping protocol for cfDNA and bioinformatics pipeline to distinguish maternal and fetal genotypes from cfDNA sequencing reads. We aim to develop and validate a non-invasive method for fetal HLA genotyping from maternal blood cfDNA collected at 10-20 weeks of pregnancy using a probe panel for hybrid capture enrichment and sequencing on the Illumina platform, validated with maternal, paternal, and fetal samples. In addition, we propose to develop and validate a high-resolution fetal KIR genotyping protocol from maternal cfDNA, addressing the challenges of structural variation and sequence homology in the KIR region and validating it with maternal-fetal dyads and trios. Upon completion, we expect to have a validated high-resolution fetal KIR-HLA genotyping protocol, facilitating the development of a prognostic biomarker for fetal-maternal health.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $436,100 )
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Child Health and Human Development Extramural Research	001	1	8/10/2026	NEW	$0
2026	2026	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Child Health and Human Development Extramural Research	000	1	8/6/2026	NEW	$436,100
														Subtotal = $436,100

Grand Total All Awards = $436,100

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Non-invasive fetal HLA and KIR genotyping of cell-free DNA from maternal blood

Award Number: R21HD118554

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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