<p>Osteoporosis and fractures are debilitating
skeletal problems. Accumulating the highest peak bone mass in both cortical and
trabecular bone (Tb) as well as developing strong Tb microarchitecture play an
integral role in preventing bone loss and osteoporotic fractures later in life.
Because Tb is modulated by
genetics (G) and environment (e.g. diet, D), my dissertation research
focuses on the influence of dietary calcium (Ca) intake, genetics as well as
GxD interaction controlling Tb phenotypes in two clinically relevant skeletal
sites, i.e. the femur and the L5 vertebra. Male mice from 11 in bred lines and 51 BXD recombinant
inbred (RI) lines were fed either adequate (Basal, 0.5%) or low (0.25%) Ca
diets from 4-12 weeks of age. We used micro-computed tomography to measure Tb mass
and microarchitecture phenotypes. We systematically proved that there are
site-specific effects of diet, genetic, and GxD interactions influencing Tb
phenotypes. This indicates that there are unique genetic effects modulating Tb
at each bone site. Therefore, we conducted a genetic mapping experiment using
the 51 BXD RI lines separately for each bone site. We coupled genetic mapping
analysis with bioinformatics analysis to identify novel genetic variation and
candidate genes accounting for the variation in each phenotypes. The findings
from this work serve as a
foundation for future research to identify novel pathways and genes underlying
the development of Tb as well as an adaptation to Ca insufficiency.</p>
<br>
<p> </p>
| Identifer | oai:union.ndltd.org:purdue.edu/oai:figshare.com:article/9037445 |
| Date | 13 August 2019 |
| Creators | Krittikan Chanpaisaeng (7013240) |
| Source Sets | Purdue University |
| Detected Language | English |
| Type | Text, Thesis |
| Rights | CC BY 4.0 |
| Relation | https://figshare.com/articles/The_Site-specific_Influence_of_Gene-by-diet_Interactions_on_Trabecular_Bone_in_Male_Mice/9037445 |
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