A common flanking variant is associated with enhanced meiotic stability of the FGF14-SCA27B locus

Pellerin, D.; Del Gobbo, G.; Couse, M.; Dolzhenko, E.; Dicaire, M.-J.; Rebelo, A.; Roth, V.; Wandzel, M.; Bonnet, C.; Ashton, C.; Lamont, P. J.; Laing, N. G.; Renaud, M.; Ravenscroft, G.; Houlden, H.; Synofzik, M.; Eberle, M. A.; Boycott, K. M.; Pastinen, T.; Brais, B.; Zuchner, S.; Danzi, M. C.

doi:10.1101/2023.05.11.540430

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bioRxiv · 10.1101/2023.05.11.540430

A common flanking variant is associated with enhanced meiotic stability of the FGF14-SCA27B locus

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Abstract

The factors driving initiation of pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14-SCA27B (GAA)*(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a 5-flanking 17-bp deletion-insertion in 70.34% of alleles (3,463/4,923). This common sequence variation was present nearly exclusively on alleles with fewer than 30 GAA-pure repeats and was associated with enhanced meiotic stability of the repeat locus.

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Pellerin, D., Del Gobbo, G., Couse, M., Dolzhenko, E., Dicaire, M.-J., Rebelo, A., Roth, V., Wandzel, M., Bonnet, C., Ashton, C., Lamont, P. J., Laing, N. G., Renaud, M., Ravenscroft, G., Houlden, H., Synofzik, M., Eberle, M. A., Boycott, K. M., Pastinen, T., Brais, B., Zuchner, S., Danzi, M. C.. 2023-05-14. A common flanking variant is associated with enhanced meiotic stability of the FGF14-SCA27B locus. https://doi.org/10.1101/2023.05.11.540430

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