Genetics Core

Mayo Clinic Rochester, Rochester MN

Investigators

Linked publications & trials

Abstract

ABSTRACT – ALLFTD2: GENETICS CORE Ultimately, deep knowledge on the complete mutational basis for frontotemporal lobar degeneration (FTLD) in individual patients, including those with familial FTLD, will be crucial to accurately target the underlying biological cause(s) and select the most appropriate participants for clinical trials and future therapies. To address the rapidly evolving genetic FTLD landscape we propose a comprehensive approach to identify and evaluate a wide range of genetic contributions to help disentangle FTLD etiology. Given the fundamental role of genetics in the etiology and pathophysiology of FTLD, the overall goal of the Genetics Core (GC) is to generate, analyze, and interpret genetic data from all ARTFL LEFFTDS Longitudinal FTLD (ALLFTD) participants to support research within all projects and cores and, other researchers in the field. Since the inception of the ARTFL and LEFFTDS studies in 2014, the GC has successfully generated and analyzed genetic data from more than 2,350 participants; with approximately an additional 1,050 new participants expected to be enrolled during the next cycle, bringing the total to over 3,400 participants with DNA available for genetic studies. The GC will continue to play a vital role in ALLFTD2, by stratifying newly enrolled participants into genetically homogenous subgroups for use in downstream clinical, imaging and biomarker analyses, by deep genetic profiling of unexplained FTLD patients, and by its active role not only in the genotyping but also in the identification of the most relevant polygenic scores (PGS) and genetic modifiers for use in predictive modelling studies. As part of this GC, we will conduct whole genome sequencing to provide individual genetic data, including disease-causing single nucleotide variants, small insertion and deletions, copy number variants, and repeat expansions, as well as common and rare risk and modifier variants, and PGS on all participants to support research within all cores and projects. We will also leverage our unique position to bridge the genetic FTLD community and take the lead on the identification of genetic modifiers in FTLD-GRN and collaborate on similar efforts in C9orf72-disease.