Summary
Given the major importance of the COVID-19 pandemic, with >3M cases and >130K deaths in the USA alone, and potential vulnerability of people with Down syndrome (DS; trisomy 21), we propose here to elucidate biological, genetic and epigenetic factors that can influence the response to SARS-CoV-2 in people with DS. We will map DNA methylation patterns and assess gene expression in chromosomal regions that are genetically and biologically linked to the COVID-19 host response, comparing these patterns in immune system cells from people with DS to those in age-matched control individuals, we will engineer CRISPR/Cas9-mediated deletions in the strongest differentially methylated sequences and measure effects on gene expression, we will develop an accurate and experimentally tractable mouse model of COVID-19 in DS, and quantitate age-dependence of methylation of the host response genes both in humans and in this well controlled model system. We expect our findings to lead to improved clinical and public health management of COVID-19 both in DS and in the general population.
Down Syndrome Publications
Progress in brain research2020