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Functional Analysis of the Anti-Müllerian Hormone as a Convergently Acquired Master Sex Determination Gene

Award Number: R01GM147312
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: 04/01/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028

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Functional Analysis of the Anti-Müllerian Hormone as a Convergently Acquired Master Sex Determination Gene - PROJECT SUMMARY Development of separate sexes is a fundamental process throughout vertebrates. In many species, male and female differentiation is triggered early during embryogenesis by a master sex determination (MSD) gene that resides on the Y chromosome. Although sex differentiation is a remarkably conserved process among vertebrates, the MSD gene that initiates the process is incredibly variable. It remains unclear how a diverse assortment of MSD genes integrates with the canonical vertebrate sex differentiation network. A clear understanding of the genetic regulation of sex determination and differentiation is essential because disruptions in this process can lead to several disorders of sexual development. Our long-term goals are to use the diverse types of sex chromosomes among closely related species of stickleback fish to determine how anti-Müllerian hormone (Amh) has been repeatedly co-opted into a role as an MSD gene. Work in my lab has established stickleback fish as a premier vertebrate model system to understand how sex chromosomes and sex determination evolves. We have identified the independent acquisition of a Y-linked Amh (Amhy) in two species of stickleback fish that evolved through separate duplications and translocations. Our central hypothesis is that sex-linked copies of Amh (Amhy) can elicit a similar transcriptional response in the sex differentiation network across species. This occurs once duplicates have independently gained regulatory elements necessary for expression during early primordial gonad development. In this proposal we will use an innovative combination of functional genetics and comparative genomics to explore our hypothesis through three aims: (1) Determine if Amhy is necessary and sufficient for male development in threespine and brook stickleback fish, (2) Identify how Amhy is regulated during the time of sex determination, and (3) Characterize how the downstream sex differentiation regulatory network responds to the acquisition of Amhy as an MSD gene. This project will have a significant impact on the field as it will reveal the genetic mechanisms responsible for the observed plasticity in sex determination across vertebrates. This work will also lead to broader insights into the common function of Amh across vertebrates as a whole and will provide key genomic resources that will further enable stickleback fish as a leading vertebrate model system to understand how sex chromosomes evolve.


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 = $311,077 )
2025	2025	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Biomedical Research and Research Training	000	3	4/28/2025	NON-COMPETING CONTINUATION	$311,077
														Subtotal = $311,077

Issue Date FY: 2024 ( Subtotal = $311,238 )
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Biomedical Research and Research Training	001	2	6/24/2024	NON-COMPETING CONTINUATION	$31,124
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Biomedical Research and Research Training	000	2	2/27/2024	NON-COMPETING CONTINUATION	$280,114
														Subtotal = $311,238

Issue Date FY: 2023 ( Subtotal = $311,395 )
2023	2023	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 EAST CAMPUS RD TUCKER HALL ROOM 409	ATHENS	GA	30602	CLARKE	USA	Biomedical Research and Research Training	000	1	3/15/2023	NEW	$311,395
														Subtotal = $311,395

Grand Total All Awards = $933,710

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Functional Analysis of the Anti-Müllerian Hormone as a Convergently Acquired Master Sex Determination Gene

Award Number: R01GM147312

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: 04/01/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

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