Genetics and High Throughput -Omics

REVISED ABSTRACT: Genetics & High Throughput –Omics Core: Project Summary 2P30AG066444-06 (5158) Aging populations worldwide, especially in developed countries, face an increasing burden of neurodegenerative diseases, particularly Alzheimer disease (AD), Frontotemporal dementia (FTD), and other AD-related dementias (ADRDs). Genetic studies have greatly contributed to our understanding of these complex diseases. Initial studies of an inherited form of AD resulted in the identification of mutations in the genes encoding β-amyloid precursor protein (APP), Presenilin 1 (PSEN1), and Presenilin 2 (PSEN2). Mutations in Granulin (GRN), Microtubule-Associated Protein Tau (MAPT), and C9orf72 have been identified as causes of FTD. These diseases are characterized by protein misfolding and aggregation, and also share some clinical and neuropathological characteristics. The promise of the twenty-first century is that we will be able to classify these diseases by the genetic cause or genetic risk factors. Furthermore, it is clear that studies beyond genetics, such as transcriptomics, proteomics, or epigenomics, are needed to fully understand the biology of AD and ADRDs, with the intention of identifying novel biomarkers and therapeutic targets. The goal of the Genetics & High Throughput -Omics Core at the Knight ADRC is to obtain, bank, and QC biospecimens (DNA, RNA and plasma) from Knight ADRC participants. The Core is also responsible for storing and standardizing various types of data, including genome-wide association study (GWAS), whole exome sequencing (WES), whole genome sequencing (WGS), transcriptomic, proteomic, methylation, and metabolomic data obtained from Knight ADRC participants. The purpose of this is to ensure data integrity and compatibility, facilitating sharing with the scientific community. Additionally, tissue-specific biological clocks generated from methylation and proteomics data are made available. Furthermore, the Core develops web browsers that enable investigators to query multi-omic profiles from Knight ADRC participants, thus promoting broad sharing within the scientific community.