JSU Student Symposium 2021

Genetic & Evolutionary Conservation Analysis in C. elegans to Examine the Functional Conservation of Human Genes and Decipher Variants of Uncertain Significance

Title

Genetic & Evolutionary Conservation Analysis in C. elegans to Examine the Functional Conservation of Human Genes and Decipher Variants of Uncertain Significance

Date

2-11-2021

Faculty Mentor

Ashley Turner, Biology

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Files

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Submission Type

Poster

Location

Virtual

Description

Impressive technological advances in genome sequencing have surpassed our capability to interpret the clinical implications of the genetic variation we discover. The majority of genetic variants identified in patients are currently clinically classified as “variant of unknown significance (VUS),” where their causation of disease or association with disease risk are unclear. Explorations of VUS in genetically tractable model organisms, such as Caenorhabditis elegans, are integral studies for assessing the functional conservation of human genes and understanding the functional consequences of disease-associated variants. VUS tend to be missense variants that are particularly challenging for interpretation. We examined missense VUS identified in patients with a wide range of diseases with C. elegans orthologous genes, including attention deficit hyperactivity disorder, type 2 diabetes mellitus, cystinuria, and supravalvular aortic stenosis. We identified conserved missense VUS in the following human genes and orthologous C. elegans genes: DRD5 and dop-2; INSR and daf-2; PEPD and K12C11.1; SLC3A1 and atgp-2; ELN and ssq-1. Preliminary genetic and evolutionary conservation analyses suggest functional impact for some of these VUS, warranting further in vivo investigation. We are working to optimize polymerase chain reaction-based genotyping assays and phenotyping assays to generate and assess CRISPR-Cas9-engineered C. elegans models containing each VUS. These findings fuel our research pipeline that facilitates assessment of the functional conservation of human genes and structure-function analysis of disease-associated variants through CRISPR-Cas9-engineered C. elegans models with in vivo functional assays to decipher variants of uncertain significance.

Keywords

student research, biology

Rights

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Disciplines

Ecology and Evolutionary Biology

Genetic & Evolutionary Conservation Analysis in C. elegans to Examine the Functional Conservation of Human Genes and Decipher Variants of Uncertain Significance

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