CUP Undergraduate Research


Predicted Deleterious Missense Mutations and Their Contributions to the Threshold Hypothesis in the Non-Down Syndrome AVSD Population

Date of Award


Document Type

Restricted Access Thesis


College of Theology, Arts, & Sciences


Math & Science

Degree Name

Biology, BA

First Advisor

Dr. Rici Hallstrand


Atrioventricular septal defect (AVSD) is a congenital heart disease (CHD) characterized by defective atria and ventricular septa, allowing unregulated circulatory interaction between the heart chambers. Half of all Down syndrome (DS) patients have a CHD with 75% having complete AVSD, thus making them a sensitized population. This anomaly’s genetic origins are poorly understood, but cannot be solely attributed to dosage effects of DS, since half of these patients have structurally normal hearts. It has been proposed that environmental and genetic factors contribute to a threshold, which when exceeded, result in complete AVSD. Scientists are now looking for potentially deleterious mutations that contribute to this threshold, with recent results finding multiple missense mutations that have high probability scores for being potentially damaging during cardiac development. In this study, PCR and restriction enzyme digests were utilized to evaluate these mutations in a non-DS AVSD population. The COL6A2 g.37935, COL6A1 g.25793, and FBLN2 g.86236 mutations were not found in the non-DS population studied. Our results did not, therefore, support the hypothesis, suggesting that these mutations may not contribute to the threshold among this particular population. Our results might be attributed to the relatively small population sampled, whereas a larger sample may produce different findings. This study investigated a few of the potential candidate genes associated with risk of AVSD, but future experiments will aim to evaluate more, which may subsequently shed light on contributing mutations in the threshold for the DS population.

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