# Discovering New Mendelian Genes Controlling Human Reproduction Using the Human Disease Model of Isolated GnRH Deficiency (IGD)

> **NIH NIH P50** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $529,009

## Abstract

Project 1 Abstract 
Using the human disease model of Isolated GnRH Deficiency (IGD), ~35 genes that control human 
reproduction have been discovered, several from our Center. We now propose three new Specific Aims (SAs) 
to accelerate these new genes discovery efforts dramatically. SA #1 will select subsets of our IGD cohort of 
2,000+ IGD patients who: a) share a second rare phenotype; or b) are from multiplex IGD families, and provide 
them facilitated access to our whole exome sequencing (WES) pipeline in which we can define new coding 
sequence mutations. SA #2 will then use novel statistical enrichment analysis that will allow novel gene 
discovery using WES in our full IGD cohort. Similarly, this aim will also employ novel copy number variation 
(CNV) analysis pipelines to identify the role of CNVs in IGD. Finally, SA #3 will utilize whole genome 
sequencing (WGS) combined with RNA sequencing in IGD patients who: a) harbor “balanced” chromosomal 
rearrangements; or b) are from multiplex families or trios whose WES/CNV analysis were negative in order to 
define the full range of structural and non-coding variation in our IGD patients. Taken together, this 
combination of contemporary approaches, unique populations, and advances in next generation (NGS) should 
provide us with a fuller understanding of the mendelian genes that control human reproduction.

## Key facts

- **NIH application ID:** 9910432
- **Project number:** 5P50HD028138-30
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** William Francis Crowley
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $529,009
- **Award type:** 5
- **Project period:** — → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9910432

## Citation

> US National Institutes of Health, RePORTER application 9910432, Discovering New Mendelian Genes Controlling Human Reproduction Using the Human Disease Model of Isolated GnRH Deficiency (IGD) (5P50HD028138-30). Retrieved via AI Analytics 2026-06-14 from https://api.ai-analytics.org/grant/nih/9910432. Licensed CC0.

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