Genotyping TPH2 and AGT to Determine Disease Risk in a Family

Undergraduate #88
Discipline: Biological Sciences
Subcategory: Genetics

Lawrence J. Prograis, IV - Harris-Stowe State University
Co-Author(s): Scott Horrell, Harris-Stowe State University, Saint Louis, MO

Genetic testing has the ability to uncover aspects of health before problems ever arise. With genetic testing you can detect dysfunctional genes that are responsible for many aspects of health. Additionally, this could be performed on both parents and children to determine specific inherited risk. Many aspects of mental health have underlying genetic causes. Serotonin is a neurotransmitter important for the function of the nervous system. Generally it is associated with feelings of well-being and happiness. Individuals suffering from depression often have altered levels of serotonin in their brain. TPH2, tryptophan hydroxylase 2, is an important protein required for the biosynthesis of serotonin. Many individuals suffering from mental disorders have mutations in the TPH2 gene. Blood pressure is also strongly influenced by genetics. Angiotensin is a hormone that causes blood vessels to constrict. Additionally, it causes the release of aldosterone which promotes sodium retention in the kidneys driving blood pressure up. Families suffering from high blood pressure often have mutations in angiotensin genes.
The focus of our project was to develop genetic tests to identify common mutations in these genes which can predispose an individual to develop these diseases. Purifying human DNA is a cheap, simple, and quick process that we were able to perform using DNA provided by anonymous donors. Clinical histories were obtained documenting whether all subjects had histories of depression and/or hypertension. Informed consent was obtained from all subjects. We were able to design PCR-based test which were able to detect these mutations. Using this approach we were able to genotype a family (two parents and a child) for the presence of these genes. Interestingly, the presence of these mutations did not always correlate with the observed phenotype in the individuals. For example, one individual which had a faulty angiotensin gene did not have a history of high blood pressure. This suggests that the trait is dictated by far more than simply genetic background. Perhaps for this specific trait lifestyle plays a larger role in its development. It is also possible that the actions of other genes are more important than that of angiotensin. However, the inheritance of the TPH2 alleles more closely matched the phenotypes. One parent who had the mutation had a history of depressive disorders. The other parent who did not have the mutation did not report any issues with depression. Thus, the underlying genotype we have identified in these individuals matches the observed phenotype. We were also able to show that the child had inherited both alleles providing us additional proof that our genotyping is accurate. Future efforts will be directed at developing additional genetic tests to determine if they are accurate predictors of phenotype.

Funder Acknowledgement(s): I thank S. Horrell, and D. Chalker for their help and funding. Funding was also provided by a grant to D. Chalker from the National Science Foundation and an HBCU-UP grant from the National Science Foundation to Harris-Stowe State University. I would also like to thank Harris-Stowe State University for providing the opportunity and Washington University for use of their facilities.

Faculty Advisor: Scott Horrell, Horrells@hssu.edu

Role: I purified human genomic DNA. I designed the PCR tests. I performed that PCR. I analyzed the results.