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Evolution of Homologous Recombination Mechanisms

Award Number: R01GM114173
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/01/2015
PERIOD OF PERFORMANCE END DATE: 03/31/2025

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Evolution of Homologous Recombination Mechanisms - ABSTRACT Homologous recombination reshuffles genetic information between parental chromosomes generating genetic diversity and driving evolution. Recombination predominantly occurs at recombination hotspots, the narrow genomic regions where recombination frequency exceeds the frequency in the adjacent areas by up to three orders of magnitude. In some species, hotspots localize opportunistically to the regions with open chromatin configuration, such as promoters, enhancers and CpG islands. In others, including humans and mice, hotspots are routed away from these functional elements by the PRDM9 protein, protecting them from mutagenic effects of recombination. Deletion of the Prdm9 gene results in relocation of hotspots from PRDM9 binding sites back to promoters, leading to sterility or subfertility in mice and rats, but seemingly not in humans. This means that recombination-induced mutations in functional genomic elements will be passed to progeny. Furthermore, since locations of recombination hotspots change dramatically in Prdm9 mutants, the established patterns of linkage disequilibrium will be broken, leading to novel allele combinations. Therefore, investigation of the consequences of the Prdm9 loss in species that naturally lost Prdm9 through evolution is of particular interest. In this study we will map recombination hotspots in three species that lost canonical Prdm9 and examine three specific mechanisms that may define recombination landscape in such species.


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: 2024 ( Subtotal = $375,797 )
2024	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	002	8	7/24/2024	NON-COMPETING CONTINUATION	$31,021
2024	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	000	8	2/16/2024	NON-COMPETING CONTINUATION	$279,194
2024	2024	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	001	8	5/31/2024	SUPPLEMENT FOR EXPANSION	$65,582
														Subtotal = $375,797

Issue Date FY: 2023 ( Subtotal = $343,124 )
2023	2023	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	000	7	3/14/2023	NON-COMPETING CONTINUATION	$310,215
2023	2023	THE HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC.	6720A ROCKLEDGE DR	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	001	7	4/10/2023	SUPPLEMENT FOR EXPANSION	$32,909
														Subtotal = $343,124

Issue Date FY: 2022 ( Subtotal = $310,215 )
2022	2022	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	000	6	3/10/2022	NON-COMPETING CONTINUATION	$279,190
2022	2022	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	001	6	8/2/2022	NON-COMPETING CONTINUATION	$31,025
														Subtotal = $310,215

Issue Date FY: 2021 ( Subtotal = $358,393 )
2021	2021	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	000	5	3/11/2021	COMPETING CONTINUATION	$322,415
2021	2021	HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE, INC., THE	6720-A ROCKLEDGE DR STE 100	BETHESDA	MD	20817	MONTGOMERY	USA	Biomedical Research and Research Training	001	5	7/18/2021	COMPETING CONTINUATION	$35,978
														Subtotal = $358,393

Grand Total All Awards = $1,387,529

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Evolution of Homologous Recombination Mechanisms

Award Number: R01GM114173

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/01/2015

PERIOD OF PERFORMANCE END DATE: 03/31/2025

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