Defense Date

2019

Document Type

Thesis

Degree Name

Master of Science

Department

Human Genetics

First Advisor

Colleen Jackson-Cook

Second Advisor

Timothy York

Third Advisor

Rita Shiang

Abstract

Childhood sexual abuse (CSA) is a stressful life experience with lasting/far-reaching health and psychopathological consequences. Our laboratory recently identified a significantly increased frequency of acquired chromosomal anomalies (assessed using the cytokinesis-blocked micronucleus assay) in adult female twins exposed to CSA when compared to their unexposed co-twin. The primary aim of this study was to evaluate potential mechanism(s) underlying the observed increases in levels of micronuclei in an expanded group of 90 female identical twins (61 CSA+ females and 29 CSA- females [including a total of 27 MZ co-twin pairs]) using fluorescence in situ hybridization (FISH) methodologies, with PNA probes specific for the centromeric and telomeric regions of all chromosomes coupled with the standard CBMN assay, we were able to characterize the chromosomal contents of MN and, thus, gain insight into the mechanisms underlying MN formation. By scoring 100 MN per study participant for the number of centromeric signal(s) and/or telomeric signal(s) present, we categorized the MN as harboring either: (1) terminal fragments (only a telomeric signal); (2) acentric interstitial fragments (no telomeric or centromeric signal); (3) centric interstitial fragments (only a centromeric signal); or (4) an intact chromosome(s) or chromatid(s). We identified elevated frequencies of intact chromosome-derived MN in CSA+ women as compared to CSA- women (P=0.014), implicating chromosome loss as a mechanism potentially underlying the increased frequencies of MN identified in adult females with a history of CSA. MN containing fragmented chromosomes were also observed in all of the study participants evaluated; however MN containing terminal fragments and MN containing acentric interstitial fragments were seen less frequently in CSA+ women compared to CSA- women. This study represents the first time that the chromosomal contents of MN have been evaluated in individuals in the context of a psychosocial factor. As chromosomal loss and breakage contributes to the development of age-related health problems, these observations provide important insight into the biological mechanisms that may underlie the latent morbidity and psychopathology associated with childhood adversity. Future studies aimed at understanding the biological impact of early-life trauma could determine if the observed increase in acquired chromosomal abnormalities results in detectable somatic clonal mosaicism. This knowledge could ultimately be used to develop screening tools to identify individuals “at risk” for negative health outcomes in adulthood.

Rights

© Kaitlyn M Dochelli

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

12-5-2019

Included in

Genetics Commons

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