
Causative Identification of Novel Polygenic Genes Associated with Obesity in Humans
For the past 40 years, humans have been seeing a significant increase in obesity. While previous studies have shown that some monogenic traits and environmental factors can contribute to weight gain, these two aspects are unable to describe the entire landscape of weight differences. This idea has made polygenic obesity the last remaining area of research to fully understand the entirety of weight gain in humans. In collaboration with the Girirajan lab here at Penn State, the genes RUNX2 and TMEM151B in humans have been identified as a possible gene pair that can lead to lipid accumulation. Using this initial finding, I have been tasked to investigate this finding in Caenorhabditis elegans using the genes rnt-1 and ZK1067.4, which are orthologs to the human genes RUNX2 and TMEM151B, respectively.
This study was initially approached using dsRNA for both rnt-1 and ZK1067.4 prepared using conjugation-mediated double RNAi (CONJUDOR) to evenly apply RNAi to each animal. C. elegans were stained with oil red O at specific development stages to identify lipid accumulation, which were then imaged to quantify and analyze the overall area of lipid within each animal.
From these experiments, it was seen that the loss of ZK1067.4 in isolation was sufficient to cause an increase in adiposity. Additionally, the loss of both rnt-1 and ZK1067.4 was unable to produce a significant phenotype. This resulted in designing a new approach where one gene is initially lost in a mutant C. elegans strain and RNAi is applied to knockdown the other gene. From this experiment, it was seen that the loss of both rnt-1 and ZK1067.4 showed a reduction in lipid accumulation, appearing as a recovery of lipid accumulation.
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Work Title | Causative Identification of Novel Polygenic Genes Associated with Obesity in Humans |
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License | CC BY-SA 4.0 (Attribution-ShareAlike) |
Work Type | Research Paper |
Publication Date | April 25, 2024 |
Deposited | April 25, 2024 |
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