It takes the average reader 1 hour and 16 minutes to read In Silico, in Vitro, in Vivo and in Populo by Juan Lorenzo Rodriguez Flores
Assuming a reading speed of 250 words per minute. Learn more
In this dissertation we address the following questions. (1) Are common PNMT promoter SNPs associated with obesity in populo? (2) Do the associated and LD-tagged SNPs disrupt mammalian-conserved regulatory motifs predicted in silico and verified in vitro? (3) Can we replicate in vitro haplotype-specific and transcription-factor-specific regulatory effects consistent with the association? (4) Can we build an in silico model of chromaffin cell changes in response to PNMT deficiency in humans based on in vivo mRNA expression profies from PNMT KO vs WT mice? The most significant findings of this dissertation are as follows. Two common SNPs, one which destroys a Sp1 activation motif (rs3764351) and one which creates a Sox17 inhibitory motif (rs876493), together generate a low-activity PNMT promoter which is associated with obesity in European-American females. We identify the SNPs by resequencing, predict function by phylogenetic footprinting, then validate the bioinformatic prediction in EMSA and Luciferase promoter reporter assays. In a GO clustering analysis of adrenal-specific transcriptome changes in PNMT KO versus WT mice we identify an enrichment for obesity-associated and lipid metabolism genes among those differentially expressed. Together, these results present a genetic, molecular and cellular mechanism whereby the obesity-associated SNPs alter chromaffin cell function to produce the obesity phenotype. The experimental results can be used for pharmacogenomics research, while the genetic evidence can be used to help identify women at risk for obesity, a lifespan-reducing disease with prevalence> 20% in the USA.
In Silico, in Vitro, in Vivo and in Populo by Juan Lorenzo Rodriguez Flores is 75 pages long, and a total of 19,125 words.
This makes it 25% the length of the average book. It also has 23% more words than the average book.
The average oral reading speed is 183 words per minute. This means it takes 1 hour and 44 minutes to read In Silico, in Vitro, in Vivo and in Populo aloud.
In Silico, in Vitro, in Vivo and in Populo is suitable for students ages 8 and up.
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