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Genetic diversity in oxytocin receptor sequence, neural expression, and social behavior.

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Genetic diversity in oxytocin receptor sequence, neural expression, and social behavior./
Author:	King, Lanikea B.
Description:	1 online resource (123 pages)
Notes:	Source: Dissertation Abstracts International, Volume: 77-04(E), Section: B.
Subject:	Neurosciences. -
Online resource:	click for full text (PQDT)
ISBN:	9781339258935

Genetic diversity in oxytocin receptor sequence, neural expression, and social behavior.
King, Lanikea B.

Genetic diversity in oxytocin receptor sequence, neural expression, and social behavior. - 1 online resource (123 pages)

Source: Dissertation Abstracts International, Volume: 77-04(E), Section: B.

Thesis (Ph.D.)--Emory University, 2015.

Includes bibliographical references

Oxytocin (OXT) is a neuropeptide with conserved functions in reproductive physiology and social cognition through signalling with a single receptor, OXTR. OXTR expression occurs in diverse distributions within the brain and influences species-typical behavior. The socially monogamous prairie vole has high OXTR density in the nucleus accumbens (NAcc) compared to non-monogamous vole species. OXT and dopamine signalling converge in the prairie vole NAcc, enabling social attachments to distinct individuals. OXTR diversity in the NAcc also contributes to individual variation in prairie vole social behavior. Thus, regulatory elements (cis-REs) that influence transcription of the oxtr gene or synthesis of OXTR must be susceptible to variation. This dissertation examines the hypothesis that transcription of the prairie vole oxtr is modulated by polymorphic cis-REs. I found that a molecular signature of polymorphic cis-RE activity, allelic imbalance, occurs robustly and specifically in the NAcc. The single nucleotide polymorphism (SNP) marker used for allelic imbalance, NT204321, predicts OXTR density in the NAcc. NT204321 genotype groups also exhibit differences in mRNA levels in the NAcc and mRNA and OXTR binding are correlated in the NAcc. NT204321 also predicts individual differences in prairie vole social attachment. I next attempted to identify putative locations of cis-REs using next-generation sequencing and found approximately 3,000 SNPs within the oxtr locus. I discovered that SNPs in the prairie vole oxtr are in strong linkage disequilibrium (LD) with each other. One of these SNPs, which is located in the single intron, outperforms NT204321 as a marker of NAcc OXTR density, explaining 75% or more density variation in three separate replicates. Future studies using the intron SNP will investigate gene by environment interactions and probe more deeply into the mechanisms influence oxtr regulation.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2018

Mode of access: World Wide Web

ISBN: 9781339258935Subjects--Topical Terms:

593561
Neurosciences.
Index Terms--Genre/Form:

554714
Electronic books.

Genetic diversity in oxytocin receptor sequence, neural expression, and social behavior.
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504 $a Includes bibliographical references
520 $a Oxytocin (OXT) is a neuropeptide with conserved functions in reproductive physiology and social cognition through signalling with a single receptor, OXTR. OXTR expression occurs in diverse distributions within the brain and influences species-typical behavior. The socially monogamous prairie vole has high OXTR density in the nucleus accumbens (NAcc) compared to non-monogamous vole species. OXT and dopamine signalling converge in the prairie vole NAcc, enabling social attachments to distinct individuals. OXTR diversity in the NAcc also contributes to individual variation in prairie vole social behavior. Thus, regulatory elements (cis-REs) that influence transcription of the oxtr gene or synthesis of OXTR must be susceptible to variation. This dissertation examines the hypothesis that transcription of the prairie vole oxtr is modulated by polymorphic cis-REs. I found that a molecular signature of polymorphic cis-RE activity, allelic imbalance, occurs robustly and specifically in the NAcc. The single nucleotide polymorphism (SNP) marker used for allelic imbalance, NT204321, predicts OXTR density in the NAcc. NT204321 genotype groups also exhibit differences in mRNA levels in the NAcc and mRNA and OXTR binding are correlated in the NAcc. NT204321 also predicts individual differences in prairie vole social attachment. I next attempted to identify putative locations of cis-REs using next-generation sequencing and found approximately 3,000 SNPs within the oxtr locus. I discovered that SNPs in the prairie vole oxtr are in strong linkage disequilibrium (LD) with each other. One of these SNPs, which is located in the single intron, outperforms NT204321 as a marker of NAcc OXTR density, explaining 75% or more density variation in three separate replicates. Future studies using the intron SNP will investigate gene by environment interactions and probe more deeply into the mechanisms influence oxtr regulation.
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