- Library Home /
- Search Collections /
- Open Collections /
- Browse Collections /
- UBC Theses and Dissertations /
- X-chromosome inactivation patterns in human extraembryonic...
Open Collections
UBC Theses and Dissertations
UBC Theses and Dissertations
X-chromosome inactivation patterns in human extraembryonic and fetal tissues Peñaherrera Arcos, Maria Serena
Abstract
X-chromosome inactivation (XCI) compensates for dosage of X-linked genes in female mammals. XCI is generally random and clonally inherited in embryonic tissues, XCI patterns in the placenta appear to be distinct and vary among different mammalian species. The aim of this thesis was to further our understanding of XCI patterns in human placentae with three main goals: 1) To determine if XCI shows a parental bias in human placenta as it does in mouse and other mammals, XCI patterns were studied in amnion, chorion, trophoblast and mesenchyme of 14 normal female term placentae, and 11 first trimester placentae using methylation based assays (AR and FMR-1). XCI patterns were heterogeneous within most term placentae, in both direction and degree of skewing, indicating that there is no clear parental bias to XCI in term placentae. However, a trend towards the preferential inactivation of the paternally derived X was observed in trophoblast of first trimester placentae. Investigation of a placenta with a paternally derived X/autosome translocation also supports the idea that preferential inactivation of the paternal X is probably not a requirement for normal development in humans as it is in mice. 2) To determine whether all or most X-linked genes are hypomethylated in human extraembryonic tissues, XCI was studied in 20 CVS samples, using methylation-based assays for 7 X-linked genes (MAOA, ARAF, AR, XIST, DXS6673E, GRIA3E and FMR-1). Incomplete methylation was observed for all genes except XIST. The low methylation suggests either gene derepression, or that an alternative mechanism of silencing is involved in gene regulation in placenta. 3) To use XCI studies to understand the characteristics of cell dynamics in cases of trisomy preferentially confined to the placenta, I studied XCI in embryonic and extraembryonic tissues from 25 such cases. Extremely skewed XCI was found in diploid fetal but not placental tissues of most of these individuals. This may result from the selective elimination of trisomic cells from the embryonic precursor cell pool subsequent to XCI. A significant correlation between high levels of skewing and abnormal fetal outcome was evident, suggesting that when high levels of trisomy are found in the placenta, there is an increased probability of "hidden" trisomy mosaicism in the fetus.
Item Metadata
Title |
X-chromosome inactivation patterns in human extraembryonic and fetal tissues
|
Creator | |
Publisher |
University of British Columbia
|
Date Issued |
2002
|
Description |
X-chromosome inactivation (XCI) compensates for dosage of X-linked genes in
female mammals. XCI is generally random and clonally inherited in embryonic tissues, XCI
patterns in the placenta appear to be distinct and vary among different mammalian species.
The aim of this thesis was to further our understanding of XCI patterns in human placentae
with three main goals:
1) To determine if XCI shows a parental bias in human placenta as it does in
mouse and other mammals, XCI patterns were studied in amnion, chorion, trophoblast and
mesenchyme of 14 normal female term placentae, and 11 first trimester placentae using
methylation based assays (AR and FMR-1). XCI patterns were heterogeneous within most
term placentae, in both direction and degree of skewing, indicating that there is no clear
parental bias to XCI in term placentae. However, a trend towards the preferential
inactivation of the paternally derived X was observed in trophoblast of first trimester
placentae. Investigation of a placenta with a paternally derived X/autosome translocation also
supports the idea that preferential inactivation of the paternal X is probably not a requirement
for normal development in humans as it is in mice.
2) To determine whether all or most X-linked genes are hypomethylated in human
extraembryonic tissues, XCI was studied in 20 CVS samples, using methylation-based assays
for 7 X-linked genes (MAOA, ARAF, AR, XIST, DXS6673E, GRIA3E and FMR-1).
Incomplete methylation was observed for all genes except XIST. The low methylation
suggests either gene derepression, or that an alternative mechanism of silencing is involved
in gene regulation in placenta.
3) To use XCI studies to understand the characteristics of cell dynamics in cases
of trisomy preferentially confined to the placenta, I studied XCI in embryonic and
extraembryonic tissues from 25 such cases. Extremely skewed XCI was found in diploid fetal
but not placental tissues of most of these individuals. This may result from the selective
elimination of trisomic cells from the embryonic precursor cell pool subsequent to XCI. A
significant correlation between high levels of skewing and abnormal fetal outcome was
evident, suggesting that when high levels of trisomy are found in the placenta, there is an
increased probability of "hidden" trisomy mosaicism in the fetus.
|
Extent |
15518239 bytes
|
Genre | |
Type | |
File Format |
application/pdf
|
Language |
eng
|
Date Available |
2009-11-12
|
Provider |
Vancouver : University of British Columbia Library
|
Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
|
DOI |
10.14288/1.0091200
|
URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
|
Graduation Date |
2003-05
|
Campus | |
Scholarly Level |
Graduate
|
Aggregated Source Repository |
DSpace
|
Item Media
Item Citations and Data
Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.