22q11 Deletion Syndrome: B-cell Gene Expression Profiles and Potential Links to ASD and Schizophrenia Open Access

Abstract

22q11.2 Deletion Syndrome (22q11DS) is associated with diverse neurobehavioral characteristics including mild intellectual impairment, reduced spatial reasoning, delayed speech and motor development, lowered executive functioning, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder. There is substantial-inter-individual variation in the neuropsychiatric challenges faced by these patients. Importantly, up to 30% of people with 22q11DS are diagnosed with schizophrenia by adulthood. The interaction of genetic and environmental factors and their impact on neurodevelopment is not yet understood. This study compared B-cell expression profiles of 12 individuals with 22q11DS and 12 controls in a RNA microarray to i) examine expression levels of genes in 22q11 deletion region ii) examine differentially expressed genes using Ingenuity Pathways Analysis (IPA) software to determine significant cellular and metabolic pathways iii) test for an association between expression of significant genes and externalizing and internalizing behavior. IPA analysis revealed that ubiquitination pathways played a central role in molecular networks predicted by our differential gene expression patterns. Disruptions in the ubiquitination pathway have previously been associated with idiopathic schizophrenia. A dysregulated gene in our study, UFD1L, may be a link to the etiology of this disease among 22q11 individuals. Other dysregulated genes include HGF and BASP1, associated with ASD and idiopathic schizophrenia respectively. No significant relationship between expression levels and behavior was found. This study uncovers potential mechanisms by which disruption of complex molecular pathways can lead to ASD or schizophrenia in this high-risk population.

Table of Contents

Table of Contents Introduction.....................1 Background......................4 Methods.........................11 Results...........................17 Discussion.......................21 References......................25 Tables............................30 Figures...........................43 Appendix........................50

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Biology, Genetics Health Sciences, Public Health Health Sciences, Epidemiology
Keyword	HGF velocardiofacial syndrome DiGeorge syndrome UFD1L BASP1 schizophrenia IPA 22q11DS 22q11 ubiquitination conotruncal anomaly face syndrome microarray ASD
Committee Chair / Thesis Advisor	Pearce, Brad, Emory University
Partnering Agencies	Emory University schools, faculty or affiliated programs

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