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Comment
. 2022 Apr 8;3(4):226-227.
doi: 10.1016/j.medj.2022.03.008.

Integrating functional genomics with genetics to understand the biology of ALS and FTD

Carlos Cruchaga  1
Affiliations
Free article
Comment

Integrating functional genomics with genetics to understand the biology of ALS and FTD

Carlos Cruchaga. Med. .
Free article

Abstract

Genetic variants in chromosome 19 are strongly associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Ma et al.1 and Brown et al.2 demonstrated that this association was driven by variation in UNC13A and that the underlying mechanism involved aberrant TDP-43 localization, a known pathological hallmark of both diseases.

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Conflict of interest statement

Declaration of interests C.C. has received research support from Biogen, EISAI, Alector, and Parabon and is a member of the advisory boards of Vivid Genetics, Halia Therapeutics, and ADx Healthcare.

Comment on

  • TDP-43 represses cryptic exon inclusion in the FTD-ALS gene UNC13A.
    Ma XR, Prudencio M, Koike Y, Vatsavayai SC, Kim G, Harbinski F, Briner A, Rodriguez CM, Guo C, Akiyama T, Schmidt HB, Cummings BB, Wyatt DW, Kurylo K, Miller G, Mekhoubad S, Sallee N, Mekonnen G, Ganser L, Rubien JD, Jansen-West K, Cook CN, Pickles S, Oskarsson B, Graff-Radford NR, Boeve BF, Knopman DS, Petersen RC, Dickson DW, Shorter J, Myong S, Green EM, Seeley WW, Petrucelli L, Gitler AD. Ma XR, et al. Nature. 2022 Mar;603(7899):124-130. doi: 10.1038/s41586-022-04424-7. Epub 2022 Feb 23. Nature. 2022. PMID: 35197626 Free PMC article.
  • TDP-43 loss and ALS-risk SNPs drive mis-splicing and depletion of UNC13A.
    Brown AL, Wilkins OG, Keuss MJ, Kargbo-Hill SE, Zanovello M, Lee WC, Bampton A, Lee FCY, Masino L, Qi YA, Bryce-Smith S, Gatt A, Hallegger M, Fagegaltier D, Phatnani H; NYGC ALS Consortium; Newcombe J, Gustavsson EK, Seddighi S, Reyes JF, Coon SL, Ramos D, Schiavo G, Fisher EMC, Raj T, Secrier M, Lashley T, Ule J, Buratti E, Humphrey J, Ward ME, Fratta P. Brown AL, et al. Nature. 2022 Mar;603(7899):131-137. doi: 10.1038/s41586-022-04436-3. Epub 2022 Feb 23. Nature. 2022. PMID: 35197628 Free PMC article.

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