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Novel population-genetic methods for localizing targets of natural selection in diverse human genomes

Award Number: R35GM139628
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY. The PI's research program in population genetics focuses on the coalescent-based inference of population his- tories from whole genomes, and the determination of genetic basis of adaptation and disease at multiple biolog- ical scales—from mutations to genes to gene subnetworks. In the genomic era, computational and statistical methods are essential for identifying candidate adaptive and disease-associated mutations in humans, in whom mapping via linkage studies is challenging and costly. State-of-the-art approaches that scan genome-wide for signatures of selection or association with phenotype state are routinely applied to samples from one homoge- neous ancestry, rely on arbitrary thresholds for interpreting results, and produce results at genomic scales that can be difficult to connect to biological mechanism (for example, analyzing linkage blocks or sliding genomic windows). Thus, despite the enormous investments made by the NIH and biobanks around the world to generate large-scale genomic datasets from diverse individuals, methods for analyzing such datasets are lagging behind. This application describes a series of projects motivated by answering three fundamental questions in human population genetics: (1) what role has balancing selection played in human adaptation? (2) to what extent has adaptive evolution versus non-adaptive processes shaped human genomes? (3) to what extent do the genetic architectures of human traits vary by ancestry? The overall strategy for future research plans draws on the PI's expertise in coalescent theory, Bayesian inference, population genetics, and statistical genetics to produce new frameworks for analyzing patterns in and evolutionary processes underlying multiethnic genomic datasets. The outcomes of the research described in this MIRA application will give new insight into the interaction between selection and dynamic population histories in generating human genetic diversity, while determining the different modes of selection shaping human phenotypes and diseases.


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: 2025 ( Subtotal = $0 )
2025	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	4	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $374,508 )
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	4	6/27/2024	NON-COMPETING CONTINUATION	$37,451
2024	2024	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	4	11/30/2023	NON-COMPETING CONTINUATION	$337,057
														Subtotal = $374,508

Issue Date FY: 2023 ( Subtotal = $374,508 )
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	3	3/24/2023	NON-COMPETING CONTINUATION	$37,451
2023	2023	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	3	12/12/2022	NON-COMPETING CONTINUATION	$337,057
														Subtotal = $374,508

Issue Date FY: 2022 ( Subtotal = $373,985 )
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	2	12/9/2021	NON-COMPETING CONTINUATION	$336,585
2022	2022	BROWN UNIVERSITY	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	001	2	7/20/2022	NON-COMPETING CONTINUATION	$37,400
														Subtotal = $373,985

Issue Date FY: 2021 ( Subtotal = $261,450 )
2021	2021	BROWN UNIVERSITY IN PROVIDENCE IN THE STATE OF RHODE ISLAND AND PROVIDENCE PLANTATIONS	1 PROSPECT ST	PROVIDENCE	RI	02912	PROVIDENCE	USA	Biomedical Research and Research Training	000	1	12/24/2020	NEW	$261,450
														Subtotal = $261,450

Grand Total All Awards = $1,384,451

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Novel population-genetic methods for localizing targets of natural selection in diverse human genomes

Award Number: R35GM139628

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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