This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison. https://genetics564.weebly.com/
What Is Gene Ontology?
Gene Ontology is an online database that uses data from all species to provide information about the function a gene does or may have in humans (and other organisms if wanted). Gene Ontology allows for a comparative genomic approach when looking at it from a phylogenetic standpoint. [1] It can provide vast information for research in showing homologous genes, other genes that act in the same place or for the same function, and possible genes that could interact with the gene of interest. [2] Gene ontology uses three levels to look at the gene’s function: organism, cellular, and molecular. [1]
Organism/Biological level: This describes the pathways that the gene is involved in. Protein products could be at any part of the pathway and could be involved in multiple pathways. There has to be multiple steps in this pathway. [3,4]
Cellular level: This describes the location in the cell that the gene product acts in or on. [3,4]
Molecular level: This describes the specific role that the protein product of a gene carries out (in the pathway described in the biological level). These roles could be involved in catalysis, signaling, interaction with other proteins, and a variety of other functions. [3,4]
Organism/Biological level: This describes the pathways that the gene is involved in. Protein products could be at any part of the pathway and could be involved in multiple pathways. There has to be multiple steps in this pathway. [3,4]
Cellular level: This describes the location in the cell that the gene product acts in or on. [3,4]
Molecular level: This describes the specific role that the protein product of a gene carries out (in the pathway described in the biological level). These roles could be involved in catalysis, signaling, interaction with other proteins, and a variety of other functions. [3,4]
DBT at the Cellular Level
DBT at the Molecular Level
DBT at the Biological Level
Disscussion
It is clear from the cellular, molecular, and biological levels of gene ontology that the DBT gene is involved in metabolic function, specifically valine, leucine, and isoleucine degradation. Since DBT localizes in the mitochondria and is not found anywhere else in the cell, it is indicative that it is involved in energy production. This is confirmed through molecular and biological function because it produces Acytyl-CoA, which will then be used in later pathways, including the citric acid cycle (see Biological Level Image). This function has been well known for decades and is fairly conserved among species as metabolism in general is a conserved function.
Mitochondrial disorders can cause GERD [6,7], so knowing that DBT localizes in the mitochondria, points to a hypothesis that mitochondrial dysfunction caused by DBT will also cause GERD or similar symptoms. This could be contributing to the poor feeding phenotype.
The biological function can be used to determine what downstream functions may be affected. Protein and transcript levels and interactions that are affected could be contributing to the poor feeding phenotype.
Mitochondrial disorders can cause GERD [6,7], so knowing that DBT localizes in the mitochondria, points to a hypothesis that mitochondrial dysfunction caused by DBT will also cause GERD or similar symptoms. This could be contributing to the poor feeding phenotype.
The biological function can be used to determine what downstream functions may be affected. Protein and transcript levels and interactions that are affected could be contributing to the poor feeding phenotype.
References:
[1] The Gene Ontology Consortium. (2019). About the GO. Retrieved from: http://geneontology.org/docs/introduction-to-go-resource/
[2] du Plessis, L., Skunca, N., & Dessimoz, C. (2011). The what, where, how and why of gene ontology--a primer for bioinformaticians. Briefings in bioinformatics. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220872/#!po=25.0000
[3] n.a. (n.d.) An introduction to the Gene Ontology. Retrieved from ftp://ftp.geneontology.org/go/www/GO.doc.shtml#top
[4] The Gene Ontology Consortium. (2019). Gene ontology overview. Retrieved from http://geneontology.org/docs/ontology-documentation/
[5] Human Protein Atlas. (n.d.) DBT. Retrieved from https://www.proteinatlas.org/ENSG00000137992-DBT/cell
Kegg: Kyoto Encyclopedia of Genes and Genomes; https://www.genome.jp/kegg/kegg2.html
[6] Gilles, Hepple, & T., R. (2016, September 20). Editorial: Mitochondria in Skeletal Muscle Health, Aging and Diseases. Retrieved from https://www.frontiersin.org/articles/10.3389/fphys.2016.00446/full[7] Finsterer, J., & Frank, M. (2016). Gastrointestinal manifestations of mitochondrial disorders: a systematic review. Therapeutic advances in gastroenterology. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330602/
Images:
Header: cat4.jpg
[1] The Gene Ontology Consortium. (2019). About the GO. Retrieved from: http://geneontology.org/docs/introduction-to-go-resource/
[2] du Plessis, L., Skunca, N., & Dessimoz, C. (2011). The what, where, how and why of gene ontology--a primer for bioinformaticians. Briefings in bioinformatics. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3220872/#!po=25.0000
[3] n.a. (n.d.) An introduction to the Gene Ontology. Retrieved from ftp://ftp.geneontology.org/go/www/GO.doc.shtml#top
[4] The Gene Ontology Consortium. (2019). Gene ontology overview. Retrieved from http://geneontology.org/docs/ontology-documentation/
[5] Human Protein Atlas. (n.d.) DBT. Retrieved from https://www.proteinatlas.org/ENSG00000137992-DBT/cell
Kegg: Kyoto Encyclopedia of Genes and Genomes; https://www.genome.jp/kegg/kegg2.html
[6] Gilles, Hepple, & T., R. (2016, September 20). Editorial: Mitochondria in Skeletal Muscle Health, Aging and Diseases. Retrieved from https://www.frontiersin.org/articles/10.3389/fphys.2016.00446/full[7] Finsterer, J., & Frank, M. (2016). Gastrointestinal manifestations of mitochondrial disorders: a systematic review. Therapeutic advances in gastroenterology. Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5330602/
Images:
Header: cat4.jpg