# Deciphering the Role of Copy Number Variants in Neuroendocrine Disorders of Infertility

> **NIH NIH F32** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $72,502

## Abstract

PROJECT ABSTRACT
Despite 6-12% of women and men around the world suffering from infertility, the full ensemble of genes that
control human reproduction has not been fully characterized. In this study, the PI will study the genetic
background of Idiopathic Hypogonadotropic Hypogonadism (IHH), a rare neuroendocrine disorder caused by
defects in Gonadotropin Releasing Hormone (GnRH) neuronal signaling, that leads to delayed puberty and
infertility. The genetic etiology in 60% of IHH patients remains unknown. This missing heritability can be attributed
to poor characterization of elusive genetic variation such as copy number variants (CNVs) that are hard to
capture using traditional sequencing technologies, such as karyotypes and microarrays. Recent advantages in
next generation sequencing have allowed detection of smaller CNVs from exome sequencing (ES) data. In this
study, the PI will utilize such cutting edge CNV calling algorithms in a large cohort of IHH subjects (1,400) to
examine the contribution of CNVs to the missing heritability of IHH, understand the GnRH neuronal biology and
decipher the genetic control of rare and common reproductive disorders. The PI will explore the contribution of
CNVs to known and novel IHH genes and will utilize human phenotypes from the IHH patients and subjects
enrolled to the Mass General Brigham biobank (in whom CNVs from ES will be called) to determine the
consequences of CNVs in human disease expression. The PI will complete the proposed work under the
mentorship of Dr. Seminara, Dr. Talkowski and Dr. Balasubramanian. Dr. Seminara is the PI of a NICHD-
sponsored P50 National Center of Translational Research in Reproduction and Infertility (NCTRI) – Center for
Reproductive Medicine (CRM) at the Massachusetts General Hospital (MGH) and will provide all available
resources (access to ES and phenotypic databases) for the successful completion of his research proposal as
well as direct mentorship to facilitate her transition to an independent career as a physician scientist. Dr.
Talkowski is the Director for the Center of Genomic Medicine (CGM) at MGH and has pioneered novel CNV
approaches. Under his guidance, the PI will analyze ES derived CNVs in IHH, control and biobank subjects. Dr.
Talkowski is also the Director of the Genomics Core that houses all the resources for the functional validation of
the novel genes that will emerge from the PI’s CNV analyses (IPSc derived GnRH cells). Finally, Dr.
Balasubramanian is the Assistant Director of the NCTRI-CRM with significant expertise in studying population
biobanks for human genetic investigations and will provide important guidance to the PI for the successful
completion of her proposal. In addition, the candidate will pursue formal coursework and regular engagement in
research meetings related to both reproductive endocrinology and genetics. This project will facilitate
development of skills in the areas of clinical investigation and human genetics and represents a...

## Key facts

- **NIH application ID:** 10463237
- **Project number:** 1F32HD108873-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Maria Stamou
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $72,502
- **Award type:** 1
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463237

## Citation

> US National Institutes of Health, RePORTER application 10463237, Deciphering the Role of Copy Number Variants in Neuroendocrine Disorders of Infertility (1F32HD108873-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10463237. Licensed CC0.

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