Monday, June 30, 2025 6/30/2025

Search for new genes involved in male infertility through novel approaches

Award Number: R01HD106056
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: 02/22/2022
PERIOD OF PERFORMANCE END DATE: 11/30/2026

Group Awards By:

View Award Description

Search for new genes involved in male infertility through novel approaches - SUMMARY To date, the etiology of idiopathic male infertility is not fully understood, and hormonal male contraceptives have not been effective. Through novel approaches to sequencing and sequencing analysis of male infertile patients and controls, this proposal seeks to identify new coding and non-coding genes and genomic regions required for male fertility and to validate the functional requirement of newly identified genes through mouse models. Past limited sequencing-based approaches have so far only been able to provide diagnostic variants to 1.5% of infertile men who present to the clinic, a yield that will improve with identification of more genes underlying infertility in men. One limitation to past progress has been the inability of conventional short-read sequencing to resolve haplotype-specific information: whether two or more mutations in each gene are on the same or separate alleles. Since gene loss-of-function typically requires damage to both alleles, it is of paramount importance to be able to resolve this information. Through long-read sequencing (a newly established and validated technology) we will identify novel damaging mutations at haplotype-specific resolution, correlating multiple novel damaging mutations with potential loss-of-function in our newly sequenced patients. Additionally, since sperm are haploid and previous studies have demonstrated a requirement for newly synthesized genes after meiosis, we will identify mutations lethal to sperm development through sequencing of both whole blood and sperm. Mutations present in blood (representing both maternal and paternal genomes) that are absent in sperm [with haploid genomes representing 8 million (2^23) chromosome combinations] demonstrate a requirement for those genes in the later stages of sperm development. Thus, through our proposed work we will identify for the first-time genes required for male fertility in men who may in fact be fertile. Lastly, we will apply CRISPR/Cas9 in mice to validate the functional requirement of candidate genes that we identify through our sequencing studies. Novel male infertility associated genes that are found to be expressed in sperm or epididymal cells, are evolutionarily conserved in vertebrates, including mice and humans, and rank among the highest in our patients will be prioritized for validation. We will assess the fertility phenotype of mutant mice and further explore molecular pathophysiology, which for some genes may determine candidacy as a contraceptive target.


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 = $543,646 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	4	4/15/2025	NON-COMPETING CONTINUATION	$54,366
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	4	10/30/2024	NON-COMPETING CONTINUATION	$489,280
														Subtotal = $543,646

Issue Date FY: 2024 ( Subtotal = $540,499 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	3	11/9/2023	NON-COMPETING CONTINUATION	$491,362
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	3	5/2/2024	NON-COMPETING CONTINUATION	$49,137
														Subtotal = $540,499

Issue Date FY: 2023 ( Subtotal = $549,989 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	001	2	2/7/2023	NON-COMPETING CONTINUATION	$55,000
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	2	11/22/2022	NON-COMPETING CONTINUATION	$494,989
														Subtotal = $549,989

Issue Date FY: 2022 ( Subtotal = $549,989 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	Child Health and Human Development Extramural Research	000	1	2/22/2022	NEW	$549,989
														Subtotal = $549,989

Grand Total All Awards = $2,184,123

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Search for new genes involved in male infertility through novel approaches

Award Number: R01HD106056

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: 02/22/2022

PERIOD OF PERFORMANCE END DATE: 11/30/2026

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer