Genome-wide transcriptome analysis in Fragile X-associated Primary Ovarian Insufficiency (FXPOI) disease Público

Abstract

Fragile X-associated primary ovarian insufficiency (FXPOI) is characterized by reduced function of ovaries that is associated with Fragile X syndrome (FXS). Women with FXPOI often experience premature ovarian failure, infertility, and menopause before age 40, as well as a heightened risk of osteoporosis and cardiovascular disease. Given its impact on infertility and its associated health problems, FXPOI has become an emerging public health topic yet the mechanisms behind FXPOI are largely unknown. In this study, we perform a genome-wide transcriptome analysis in the FXPOI mouse model to detect genes that are dysregulated in FXPOI. Using a differential expression cutoff of FDR<0.05, we find that 195 genes are significantly down-regulated and 80 genes are significantly up-regulated in the FXPOI mouse model. By performing the Gene Ontology analysis, we discover that the down-regulated genes are significantly enriched in steroid hormone regulatory processes, whereas the up-regulated genes are involved in general signaling pathways including stress response, cell communication, etc. We believe this genome-wide study reveals a comprehensive landscape of the genetic architecture of FXPOI, which will provide an excellent opportunity to search for genes involved in the susceptibility to ovarian dysfunction, and improve the chance to develop specific therapeutic targets for FXPOI.

Table of Contents

Chapter 1. Background and Introduction ………………………1

Introduction to FXPOI ………………………………………..………..1

FXPOI significantly impacts public health ……………………… 2

Specific Aim and Significance ………………………………………..3

Approach ………………………………………..………… 4

Chapter 2. Genome-wide transcriptome analysis reveals differential gene expression in FXPOI ……………7

RNA-sequencing applications ……………………………………….. 7

RNA-sequencing differential expression analysis ……………… 8

Chapter 3. Gene Ontology analysis identifies dysregulated biological processes in FXPOI ……………………13

Scientific background of Gene Ontology analysis ………………13

Gene Ontology analysis using the PANTHER classification system ……………… 14

Chapter 4. Discussion and Perspective ……………………… 17

List of References ………………………………………..………… 19

Appendix ………………………………………..………… 21

About this Master's Thesis

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School	Rollins School of Public Health
Department	Biostatistics
Subfield / Discipline	Biostatistics - MPH & MSPH
Degree	M.P.H.
Submission	Master's Thesis
Language	English
Research Field	Biology, Bioinformatics Health Sciences, Public Health Biology, Biostatistics
Palavra-chave	public health genome-wide study FXPOI
Committee Chair / Thesis Advisor	Wu,Hao, Emory University
Committee Members	Yu,Tianwei, Emory University

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