Mayo Clinic Laboratory and Pathology Research Roundup: Feb. 18

The Research Roundup provides an overview of the past week’s research from Mayo Clinic Laboratories consultants, including featured abstracts and a complete list of published studies and reviews.


Featured Abstract

Genome-Wide Analyses as Part of the International FTLD-TDP Whole-Genome Sequencing Consortium Reveals Novel Disease Risk Factors and Increases Support for Immune Dysfunction in FTLD

Frontotemporal lobar degeneration with neuronal inclusions of the TAR DNA-binding protein 43 (FTLD-TDP) represents the most common pathological subtype of FTLD. Mayo Clinic researchers established the international FTLD-TDP whole-genome sequencing consortium to thoroughly characterize the known genetic causes of FTLD-TDP and identify novel genetic risk factors. Through the study of 1131 unrelated Caucasian patients, they estimated that C9orf72 repeat expansions and GRN loss-of-function mutations account for 25.5% and 13.9% of FTLD-TDP patients, respectively. Mutations in TBK1 and other known FTLD genes were rare, and the disease in 57.7% of FTLD-TDP patients was unexplained by the known FTLD genes. To unravel the contribution of common genetic factors to the FTLD-TDP etiology in these patients, researchers conducted a two-stage association study comprising the analysis of whole-genome sequencing data from 517 FTLD-TDP patients and 838 controls, followed by targeted genotyping of the most associated genomic loci in 119 additional FTLD-TDP patients and 1653 controls. Researchers identified three genome-wide significant FTLD-TDP risk loci: one new locus at chromosome 7q36 within the DPP6 gene led by rs118113626, and two known loci: UNC13A, led by rs1297319 and HLA-DQA2 led by rs17219281. While HLA represents a locus previously implicated in clinical FTLD and related neurodegenerative disorders, the association signal in the study is independent from previously reported associations. Through inspection of the whole-genome sequence data for genes with an excess of rare loss-of-function variants in FTLD-TDP patients as compared to controls, researchers further discovered a possible role for genes functioning within the TBK1-related immune pathway in the genetic etiology of FTLD-TDP. Together, the study based on the largest cohort of unrelated FTLD-TDP patients assembled to date provides a comprehensive view of the genetic landscape of FTLD-TDP, nominates novel FTLD-TDP risk loci, and strongly implicates the immune pathway in FTLD-TDP pathogenesis. The study was published in Acta Neuropathologica.


Published to PubMed This Week

Kelley Luedke

Kelley Luedke

Kelley Luedke is a Marketing Channel Manager at Mayo Clinic Laboratories. She is the principle editor and writer of Insights and leads social media and direct marketing strategy. Kelley has worked at Mayo Clinic since 2013. Outside of work, you can find Kelley running, traveling, playing with her kitty, and exploring new foods.