Target-enriched sequencing of chromosome 17q21.31 in sporadic tauopathies reveals no candidate variants

Publication date: June 2018
Source:Neurobiology of Aging, Volume 66
Author(s): Cristina Razquin, Sara Ortega-Cubero, Estefania Rojo-Bustamante, Monica Diez-Fairen, Elena Lorenzo, Elena Alonso, Mario Ezquerra, Owen A. Ross, Maria Carcel, Oswaldo Lorenzo-Betancor, Alexandra I. Soto, Jeremy D. Burgess, Nilüfer Ertekin-Taner, Dennis W. Dickson, Maria A. Pastor, Eduard Tolosa, Pau Pastor
The main genetic risk factors for progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are located at chromosome 17q21.31. The identification of risk H1 subhaplotypes suggests that disease-specific variants can be identified by resequencing the 17q21.31 region (1.4 Mb) in carriers of risk H1 subhaplotypes. We hypothesized that PSP/CBD H1 subhaplotype carriers could have undergone a mutational event absent among unaffected carriers leading to the disease risk. We performed this strategy in definite PSP subjects, definite CBD subjects, and healthy controls and tried to replicate the findings in a larger PSP/CBD case-control series. In the resequencing process, 40 candidate variants were identified, but an association between PSP and rs76970862 was replicated only using an unadjusted model. Gene expression association analysis of this variant suggested no potential functional effect. Although our results failed to identify disease-associated variants, it is still possible that the risk of PSP/CBD at chromosome 17 is driven by rare variants, even in PSP/CBD H1 cases or variants located outside the capture regions.



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