Dissertation
Understanding human aneuploidy: the origin of trisomy and effect of recombination and maternal age
Washington State University
Doctor of Philosophy (PhD), Washington State University
12/2007
DOI:
https://doi.org/10.7273/000005782
Abstract
The ability to properly segregate chromosomes during meiosis is of immense
importance, as aneuploidy is a leading cause of both pregnancy loss and mental
retardation. Despite the overwhelming levels of monosomy and trisomy in humans, only
two factors have been linked to increased levels of chromosome nondisjunction,
aberrant recombination and advanced maternal age. Even with decades of research on
human aneuploidy, many questions remain regarding why humans make such an
appalling number of meiotic errors. Accordingly, in my thesis research I examined the
parental and meiotic origin of several previously understudied human trisomies and
explored a possible relationship between the two known predisposing factors,
recombination and maternal age. Specifically, I conducted analyses of the origin of
nondisjunction for trisomies 13 and 22, with data suggesting that both of these
acrocentric chromosomes nondisjoin most often during the first division of maternal
meiosis. Additionally, it appears that reduced levels of recombination contribute to
increased nondisjunction of both of these chromosomes. The addition of these
chromosomes to the pool of studied chromosomes allows for comparison of
nondisjunction origin among different human chromosomes. Evidence suggests that
the mechanism of nondisjunction may be conserved among acrocentric, but not
nonacrocentric, chromosomes.
To further explore the role of recombination in nondisjunction, the possible role of
recombination in the maternal age effect was examined. Two current models that try to
explain the relationship between recombination and maternal age are the two hit
hypothesis and production line model. Each of these hypotheses makes a different
prediction about how levels of recombination will vary with increasing maternal age.
Analysis of recombination levels in mothers of varying ages who had trisomic
conceptions suggests that the relationship is chromosome-specific with some
chromosomes following the predictions of the two hit hypothesis, some the production
line hypothesis, and some having a unique pattern.
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Details
- Title
- Understanding human aneuploidy
- Creators
- Heather Elizabeth Hall
- Contributors
- Terry Hassold (Chair) - Washington State University, Molecular Biosciences, School of
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 144
- Identifiers
- 99901054763401842
- Language
- English
- Resource Type
- Dissertation