Genetic predictors of OXTR expression in a genetically diverse group of monogamous prairie voles Público

Abstract

Oxytocin (OXT) modulates multiple elements of social behavior. Humans exhibit a large diversity of sociality, with social deficit disorders and other psychiatric illnesses existing at one extreme. It has been hypothesized that the OXT system plays a large role in influencing human social variation. Specifically, the OXT receptor (OXTR) has been implicated in impacting gradations of typical social behaviors. Previous work using the monogamous prairie vole model revealed that several perfectly-correlated single nucleotide polymorphisms (SNPs) in the oxytocin receptor gene (Oxtr) are robustly associated with differences in the concentration of OXTR in the brain, which may in turn affect behavior. However, it is still unclear which specific SNPs are the strongest predictors of OXTR density and whether or not associations with candidate SNPs generalize to the prairie vole species more broadly. This study investigated the association between genotype and OXTR concentration in the brains of 96 genetically diverse monogamous prairie voles. The sample included interbred colony voles with the addition of independent wild-caught animals. The voles were genotyped and OXTR concentration was quantified in five brain regions relevant to social behavior. After filtering, SNPs strongly predicting OXTR concentration in the nucleus accumbens (NAcc) were prioritized for subsequent analyses. This included 14 SNPs previously identified plus ten additional independent markers, the majority of which fall in the intron. Interestingly, these 24 SNPs did not have additional relationships to OXTR density in any other brain regions. When the sample was broken up into wild-caught and colony groups, the strong associations were primarily driven by the colony animals. Additionally, the presence of a sex interaction was tested within each brain region, revealing a significant effect only in the anterior olfactory nucleus. Taken together, these findings confirm the region-specificity of the SNPs and highlight the importance of finding SNPs that are likely functional candidates in both colony and wild-caught groups. Further, it adds to the story of how non-coding polymorphisms in OXTR could influence individual social variation in humans. 

Table of Contents

Table of Contents

CHAPTER 1.........................................................................................................................................1

Introduction...................................................................................................................................1

Materials and Methods..............................................................................................................9

Animals.....................................................................................................................................9

Genotyping..............................................................................................................................10

Long-range PCRs for Target Enrichment of 70kb Surrounding Oxtr.......................................10

Amplicon Library Preparation ................................................................................................11

OXTR Autoradiography...........................................................................................................11

Statistical Analysis..................................................................................................................12

Results.........................................................................................................................................13

Filtering SNPs..........................................................................................................................13

Animal Relatedness.................................................................................................................15

Brain Regions Measured..........................................................................................................17

Heritability of OXTR Expression by Brain Region...................................................................18

Sex Interactions......................................................................................................................18

SNP and OXTR Expression Association in Brain Regions.......................................................20

Colony and Wild-Caught ........................................................................................................21

Discussion....................................................................................................................................25

Conclusion...................................................................................................................................31

Bibliography.................................................................................................................................32

Supplementary Data....................................................................................................................42 

Table of Figures

Figure 1. Pruning of genetic data.....................................................................................................14

Figure 2. Relatedness of colony animals..........................................................................................16

Figure 3. Location of brain regions measured..................................................................................17

Figure 4. Sex interaction with OXTR expression..............................................................................19

Figure 5. SNP and OXTR expression association..............................................................................21

Figure 6. Comparing wild-caught to colony animals in the NAcc.....................................................24

Supplementary Figure 1. Significant sex interaction in the AON.....................................................42

Table of Tables

Table 1. Pertinent 24 SNPs................................................................................................................15

Table 2. Heritability of brain regions.................................................................................................18

Supplementary Table 1. 24 SNP data for combined animal group.....................................................43

Supplementary Table 2. 24 SNP data for colony animals...................................................................43

Supplementary Table 3. 24 SNP data for wild-caught animals..........................................................44 

About this Honors Thesis

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School	Emory College
Department	Neuroscience and Behavioral Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Biology, Neuroscience Biology, Genetics
Palabra Clave	Prairie Vole OXTR Social Behavior Individual Differences
Committee Chair / Thesis Advisor	Young, Larry, Emory University
Committee Members	Liu, Robert, Emory University Eisen, Arri, Emory University

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