Alzheimer’s Disease (AD) a progressive neurodegenerative disease that results in memory loss and affects 10-30% of individuals over age 65. Currently, there are no viable treatments, which is primarily due to a lack of understanding about the disease pathogenesis. In class, we talked about multiple genetic causes for the disease that lead to increases in and/or Tau. One gene that has been linked with AD is Presenilin (PSEN1), in which dominant gain of function mutations are thought to cause an increase in y-secretase activity . To better understand the downstream consequences of PSEN1 mutations , you decide to generate a “knock- indisease model using CRISPR. Below is the endogenous PSEN1 locus with the relative position of the disease-causing mutation (*). (1 Describe draw the transgenic construct s) that you would develop to integrate this construct using CRIPSR /Cas9 (2) indicate the approximate location in the endogenous sequence that you would cut the genome and (3) name two required properties of this sequence.
