Date of Award

5-2019

Document Type

Thesis campus only

Department

Biology

First Advisor

Jonathan M. King

Second Advisor

Matthew A. Hibbs

Abstract

Background: Rates of diabetes and obesity are continually increasing in the united states, including rates among pregnant women. An estimated 30.3 million people of all ages in the U.S. have diabetes mellitus, and approximately 12.7 million children and adolescents in the U.S. are obese (Ogden, Carroll et al. 2014, CDC 2017).

Objective: The objective of this research is to determine if maternal obesity or diabetes mellitus during pregnancy results in a change in infant DNA methylation. Additionally, if that change in DNA methylation is associated with genes related to obesity or diabetes mellites (DM) disease pathways, pathways related to comorbidities of DM and obesity, or associated with complications known to be related to fetal exposure to obesity and/or DM.

Design/Methods: A total of 69 infant/mother couplets (23 diabetes (DM), 23 obese (OB), 23 healthy weight non-diabetic (NT)) were enrolled, and cord blood samples were collected at University Health System from 2016 to 2018. DNA was purified from agranular leukocytes, treated through bisulfite conversion, and processed on an Illumina Infinium MethylationEPIC BeadChip to analyze over 850,000 different probe sites to determine methylation on a site specific basis. Data were analyzed with a R Bioconductor workflow including Probe wise analysis, and Peak wise detection (Bumphunter).

Results: 15 genes and 23 probes were identified as significantly differentially methylated between DM or obese groups and healthy weight non-diabetic groups. These genes are: CCDC110, KALRN, PAG1, GNRH1, SLC2A9, CSRP2BP, HIVEP1, RALGDS, DHX37, SCNN1D, HOOK2, LCE3C, TMEM63B, LTF, and DUSP22. Genes ranged in apparent involvement in disease pathology of interest, with HOOK2, and SLC2A9 being the most related to the conditions DM and obesity based on current research.

Conclusion(s): Maternal condition causes differential methylation of DNA near, or within, certain genes. Genes located by comparison between groups with DM or obesity, and healthy weight non-diabetic groups showed promising relatedness to several pathways and diseases which may be considered to be related to DM, obesity, and associated complications of in utero exposure to diabetic and/or obese maternal conditions.

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