University of Illinois Urbana-Champaign

Adaptation to environmental stress in the human placenta

Gundling, Jr., William Evans

Content Files
GUNDLINGJR-DISSERTATION-2019.pdf

Permalink

https://hdl.handle.net/2142/105127

Description

Title
Adaptation to environmental stress in the human placenta
Author(s)
Gundling, Jr., William Evans
Issue Date
2019-04-08
Director of Research (if dissertation) or Advisor (if thesis)
Wildman, Derek E
Doctoral Committee Chair(s)
Wildman, Derek E
Committee Member(s)
  • Bagchi, Milan K.
  • Clancy, Kathryn B.H.
  • Raetzman, Lori T.
Department of Study
Molecular & Integrative Physl
Discipline
Molecular & Integrative Physi
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2019-08-23T20:44:28Z
Keyword(s)
  • Gene Expression
  • Genomics
  • Epigenetics
  • Placenta
  • Hypoxia
Abstract
The placenta mediates fetal growth by acting as a substrate for nutrient exchange between the mother and the fetus. Environmental factors such as altitude have been shown to result in reduced maternal-fetal exchange leading to reduced birth weight. To determine if differences in gene expression maybe contributing to physiological differences between individuals at high and low altitude, we tested for differences in gene expression and DNA methylation between Andean and European placental samples from La Paz (~4,000m) and Santa Cruz, Bolivia (~400m). Among the ancestry-associated differentially expressed genes, were genes involved in inflammation and placental specific pro-angiogenic macrophages, Hofbauer cells, contributing to increased capillary growth seen among Andeans residing at high altitude. Among the altitude-associated differentially expressed genes, we saw decreased expression of genes associated with the activator protein 1 (AP-1) transcription factor pathway and increased expression of genes involved in cytotrophoblast fusion including the gene dysferlin (DYSF). Upon closer examination we noticed that DYSF had a variant (rs10166384;G/A) at a methylation site with 3 levels of DNA methylation corresponding to individual genotypes. We tested for natural selection by sequencing a ~2.5kb fragment from 90 samples and performing Tajima’s D test across the sample groups. We found that balancing selection (Tajima’s D=2.37) was acting on a ~2.5kb fragment around our variant of interest among Andeans regardless of altitude. This suggests that balancing selection acting on dysferlin maybe altering DNA methylation patterns. Also, preservation of both the A and G alleles may aide Andeans in moving between altitudes.
Graduation Semester
2019-05
Type of Resource
text
Permalink
http://hdl.handle.net/2142/105127
Copyright and License Information
Copyright 2019 William Gundling, Jr.

Owning Collections

Graduate Dissertations and Theses at Illinois PRIMARY
Graduate Theses and Dissertations at Illinois
Dissertations and Theses - Molecular and Integrative Physiology