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Adaptation to environmental stress in the human placenta
Gundling, Jr., William Evans
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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
- 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.
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