TY - JOUR
T1 - A common flanking variant is associated with enhanced stability of the FGF14-SCA27B repeat locus
AU - All of Us Research Program Long Read Working Group
AU - Pellerin, David
AU - Del Gobbo, Giulia F.
AU - Couse, Madeline
AU - Dolzhenko, Egor
AU - Nageshwaran, Sathiji K.
AU - Cheung, Warren A.
AU - Xu, Isaac R.L.
AU - Dicaire, Marie Josée
AU - Spurdens, Guinevere
AU - Matos-Rodrigues, Gabriel
AU - Stevanovski, Igor
AU - Scriba, Carolin K.
AU - Rebelo, Adriana
AU - Roth, Virginie
AU - Wandzel, Marion
AU - Bonnet, Céline
AU - Ashton, Catherine
AU - Agarwal, Aman
AU - Peter, Cyril
AU - Hasson, Dan
AU - Tsankova, Nadejda M.
AU - Dewar, Ken
AU - Lamont, Phillipa J.
AU - Laing, Nigel G.
AU - Renaud, Mathilde
AU - Houlden, Henry
AU - Synofzik, Matthis
AU - Usdin, Karen
AU - Nussenzweig, Andre
AU - Napierala, Marek
AU - Chen, Zhao
AU - Jiang, Hong
AU - Deveson, Ira W.
AU - Ravenscroft, Gianina
AU - Akbarian, Schahram
AU - Eberle, Michael A.
AU - Boycott, Kym M.
AU - Pastinen, Tomi
AU - Brais, Bernard
AU - Zuchner, Stephan
AU - Danzi, Matt C.
AU - Bateman, Emily
AU - Berngruber, Chelsea
AU - Cunial, Fabio
AU - Davis, Colleen P.
AU - Dinh, Huyen
AU - Doddapaneni, Harsha
AU - Doheny, Kim
AU - Dugan-Perez, Shannon
AU - Dutka, Tara
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/7
Y1 - 2024/7
N2 - The factors driving or preventing pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a common 5′-flanking variant in 70.34% of alleles analyzed (3,463/4,923) that represents the phylogenetically ancestral allele and is present on all major haplotypes. This common sequence variation is present nearly exclusively on nonpathogenic alleles with fewer than 30 GAA-pure triplets and is associated with enhanced stability of the repeat locus upon intergenerational transmission and increased Fiber-seq chromatin accessibility.
AB - The factors driving or preventing pathological expansion of tandem repeats remain largely unknown. Here, we assessed the FGF14 (GAA)·(TTC) repeat locus in 2,530 individuals by long-read and Sanger sequencing and identified a common 5′-flanking variant in 70.34% of alleles analyzed (3,463/4,923) that represents the phylogenetically ancestral allele and is present on all major haplotypes. This common sequence variation is present nearly exclusively on nonpathogenic alleles with fewer than 30 GAA-pure triplets and is associated with enhanced stability of the repeat locus upon intergenerational transmission and increased Fiber-seq chromatin accessibility.
UR - https://www.scopus.com/pages/publications/85198753925
U2 - 10.1038/s41588-024-01808-5
DO - 10.1038/s41588-024-01808-5
M3 - Article
C2 - 38937606
AN - SCOPUS:85198753925
SN - 1061-4036
VL - 56
SP - 1366
EP - 1370
JO - Nature Genetics
JF - Nature Genetics
IS - 7
ER -