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Defining Variation in the Natural Killer Cell Receptome in Human Populations

Award Number: R21HG012386
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/18/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Defining Variation in the Natural Killer Cell Receptome in Human Populations - ABSTRACT The overall goal of this project is to develop a comprehensive map of sequence and structural variation of the NK (natural killer) cell receptome in ancestrally diverse human populations. The two genomic regions encoding NK cell receptors, leukocyte receptor complex (LRC) and natural killer complex (NKC), house more than 90 genes with an essential role in NK cell cytotoxicity against infected and cancer cells. The complex structural variation and the high degree of sequence identity among genes within these regions have served as barriers to a comprehensive analysis in former genome-wide association and sequencing studies. With our expertise and experience in studying complex genomic variation, we will develop the most comprehensive map of sequence and structural variation of the LRC and NKC in human populations. In Specific Aim 1, we will conduct a high- throughput study entailing the complete sequencing of these two complexes using our novel and validated next- generation sequencing approach. DNA samples from 2150 samples from 18 populations, including Native Americans and admixed populations from South America, Africans, European Americans, and African Americans. Sequence data will be analyzed with our custom-designed bioinformatics pipelines. We will focus not only on gene families with a known structural variation of copy number, such as KIR (killer-cell immunoglobulin-like receptor) and LILR (leukocyte immunoglobulin-like receptors) but will analyze all common variants in all 90 NKC and LRC genes to characterize the full extent of their variation. Synergized with this approach, in Specific Aim 2, we will perform a powerful single-cell expression quantitative trait loci (eQTL) mapping of LRC and NKC by sequencing the single-cell transcriptomes of NK cells from peripheral blood mononuclear cells of 40 healthy individuals. We will identify variants associated with differential expression levels in NK cells for the initial assessment of emerging functional hypotheses. We will identify any common variants within the LRC and NKC that are associated with eQTL effects, resulting in the most comprehensive study of the NK receptome genetic variation in populations to date. This exploratory project will lay the basis for further functional studies and may ultimately lead to discovering new targets for NK cell immunotherapies.


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 = -$238 )
2026	2024	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Human Genome Research	000	3	12/17/2025	NON-COMPETING CONTINUATION	-$238
														Subtotal = -$238

Issue Date FY: 2024 ( Subtotal = $261,040 )
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Human Genome Research	001	3	7/12/2024	SUPPLEMENT FOR EXPANSION	$67,790
2024	2024	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Human Genome Research	000	3	7/11/2024	NON-COMPETING CONTINUATION	$193,250
														Subtotal = $261,040

Issue Date FY: 2023 ( Subtotal = $261,459 )
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Human Genome Research	000	2	6/28/2023	NON-COMPETING CONTINUATION	$193,669
2023	2023	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Human Genome Research	001	2	6/29/2023	SUPPLEMENT FOR EXPANSION	$67,790
														Subtotal = $261,459

Issue Date FY: 2022 ( Subtotal = $206,707 )
2022	2022	UNIVERSITY OF NORTH CAROLINA AT CHARLOTTE, THE	9201 UNIVERSITY CITY BLVD	CHARLOTTE	NC	28223	MECKLENBURG	USA	Human Genome Research	000	1	8/18/2022	NEW	$206,707
														Subtotal = $206,707

Grand Total All Awards = $728,969

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Defining Variation in the Natural Killer Cell Receptome in Human Populations

Award Number: R21HG012386

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 08/18/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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