Extended Data Fig. 5: UNC13A cryptic exon inclusion is detected in disease relevant tissues of FTLD-TDP, ALS/FTLD, ALS-TDP and ALS/AD patients, and is correlated with phosphorylated TDP-43 levels in frontal cortices of FTLD-TDP patients.
From: TDP-43 represses cryptic exon inclusion in the FTD–ALS gene UNC13A
(a) UNC13A cryptic exon expression level is significantly increased in the frontal cortices of patients with FTD and ALS/FTD clinical diagnoses (Mayo Clinic Brain Bank). GAPDH and RPLP0 were used to normalize RT-qPCR (the sample size of each group is listed under the corresponding group; two-tailed Mann-Whitney test, mean ± 95% confidence interval). The schematic on top shows the localization of the primer pair (arrows) used for the RT-qPCR assay. (b) UNC13A splice variants are observed in ALS patients with unconfirmed pathology. ALS-FTLD refers to patients who have concurrent FTD and ALS. ALS patients were categorized based on whether they carry SOD1 mutations (ALS-SOD1 (Fig. 2b) vs. ALS-TDP). ALS-AD refers to ALS patients with suspected Alzheimer’s disease. The diagnoses of these patients (NYGC) are not neuropathologically confirmed. Therefore, it is unclear whether TDP-43 mislocalization is present. (c) UNC13A cryptic exon signal is positively correlated with phosphorylated TDP-43 levels in frontal cortices of FTLD-TDP patients in Mayo Clinic Brain Bank (Spearman’s rho = 0.610, n = 90, p-values were calculated by one-sided t-test). Data points are colored according to patients’ reported genetic mutations. The correlation within each genetic mutation group and the corresponding p-value and sample size is also shown.
