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  Impact of L282R on PSEN1 Phenotype

  Lauren White and Deanna Smelley

  Alzheimer’s Disease (AD) is a type of dementia, usually affecting the memory, thinking, and behavior of individuals over the age of 65. The average life span after diagnosis is 4 to 8 years, but some can live as long as 20 years after diagnosis. During the COVID-19 pandemic, death related to Alzheimer’s and Dementia increased 16%. For our research, we were interested in the role of genetics in this disease. While most Alzheimer’s disease is not usually inherited, in previous studies most patients who developed early-onset AD possessed specific genes or gene variants that were inherited. Our research focused on the mutations in the PSEN1 gene, which codes for the Presenilin-1 protein. Presenilin-1 forms the catalytic subunit of the gamma secretase complex whose primary function is the proteolytic cleavage of the amyloid protein from the Amyloid Precursor Protein (APP). Pathogenic mutations in the PSEN1 gene often lead to an accumulation of the longer, more hydrophobic version of the Amyloid-β peptide. These accumulations are thought to cause the plaques found in the brains of patients with Alzheimer’s, leading to cerebral atrophy. We examined a PSEN1 variant of unknown significance (VUS), a missense mutation which resulted in amino acid substitution from leucine to arginine at position 282. We used YASARA protein mapping to analyze the features of this variation and completed Polyphen2 analysis to assess its pathogenicity. These will be presented along with cross species multiple sequence alignment and other variant analysis.

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  An Exploration into the Effect of T147A Clinical VUS in CTLA4

  Elin Zaman

  Viral infections have always had an impact on health conditions, COVID has been one of the more recent viral infections that has shown the unforeseen health complications which had surfaced after contracting the infection. A recent CDC study had shown a health complication of an increased risk of newly diagnosed diabetes in the 30 days following SARS-coV-2 infection. This allowed for genetic inquiry into the risk between autoimmune diseases and viral infections which had been observed and documented thoroughly. As well as inquiry into the genes of the immune system. CTLA4, located at 2q33.2, is a gene which is also known as cytotoxic Tlymphocyte associated protein 4, is among the immunoglobulin superfamily that produces a T cell inhibitory protein. This gene is a protein receptor that functions as an immune checkpoint and is vital in the immune response to viral illnesses. The mutations of the CTLA4 gene have been implicated in type 1 diabetes (DM1), autoimmune thyroiditis, celiac, lupus, Graves disease and other autoimmune illnesses. My CTLA4 variant, T174A, is a missense mutation which resulted in an amino acid switch from threonine to alanine at position 174. The bioinformatic tools of PolyPhen2, YASARA protein mapping and other analyses were utilized to assess variation pathogenicity, as well as analyze the features of this particular variant. These bioinformatic results will be presented along with cross species multiple sequence alignment and other variant analysis.