Poster Session 10 Program Schedule
02/17/2024
09:00 am - 10:15 am
Room: Shubert Complex (Posters 1-60)
Poster Session 10: Neurodevelopmental | Congenital Conditions
Final Abstract #5
Genomic Portrayal of CLCN-2 Mutations and Bipolar Disorder
Nadia Andrews, Alabama A&M University, Huntsville, United States
Elaine Vanterpool, PhD, Oakwood University, Huntsville, United States
Courtney Ray, PhD, CUNY-Brooklyn College, New York, United States
Category: Genetics/Genetic Disorders
Keyword 1: bipolar disorder
Keyword 2: genetics
Keyword 3: genetic disorders
Objective:
Bipolar disorder is typically first identified during adolescence. Symptoms include dramatic changes in mood, behavior, cognitive function, psychological health, as well as physical health. Research suggests its etiology may stem from a single genetic mutation. The chloride voltage-gated channel 2 gene (CLCN-2) is solely responsible for aiding in the creation of the CIC-2 chloride channel which is vital for neuronal functioning. CLCN-2 has five phenotypic variations that are associated with various mental disorders. Here we investigate the phenotypic expressions of this gene when functioning typically and when subjected to a missense mutation. We hypothesized that a morphologically apparent mutation on this gene is linked to bipolar disorder.
Participants and Methods:
The Simple Clinvar site was used to determine the protein mapping, phenotypic values, and variants of the CLCN-2 gene in mutation form. Search terms used were: pathogenic, likely pathogenic, benign, (clinical significance), and missense mutations (consequence).
Following this, the NCBI site was used to download the FASTA sequence of a typical CLCN-2 gene and its different isoforms. CLCN-2 genomic information was derived from a publicly available data set of RNA sequencing of 27 tissues sampled from 95 individuals.
Polyphen-2 simulation was used to model the phenotypic representation of a healthy CLCN-2 gene versus a mutated one when proteins were switched at various locations. The phenotypic representation of a healthy CLCN-2 gene was compared to the newly mutated CLCN-2 gene at various sites.
Results:
The examination of the genetic structures revealed a correlation between isoform 5 or isosine-5 and mutations on the CIC-2 chloride channel protein in individuals with bipolar disorder. This link is thought to be associated with an increased risk of developing bipolar disorder.
Conclusions:
Bipolar disorder is a complex and debilitating mental illness believed to have a strong genetic component. The identification of specific genetic mutations that contribute to the development of the disorder is a critical step in improving our understanding of its pathophysiology and developing more effective treatments.
Methods followed in this study, including the analysis of genetic data from individuals with bipolar disorder to identify the presence of CLCN-2 mutations, have the potential to greatly enhance our knowledge of the role of this gene in the development of the disorder. Identifying specific genetic changes associated with bipolar disorder has the potential to not only enhance our understanding of its genetic basis but also aid in the development of targeted treatments that address specific molecular mechanisms underlying the disease.
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