TY - JOUR
T1 - Analysis of mutational dynamics at the DMPK (CTG)n locus identifies saliva as a suitable DNA sample source for genetic analysis in myotonic dystrophy type 1
AU - Corrales, Eyleen
AU - Vásquez, Melissa
AU - Zhang, Baili
AU - Santamaría-Ulloa, Carolina
AU - Cuenca, Patricia
AU - Krahe, Ralf
AU - Monckton, Darren G.
AU - Morales, Fernando
N1 - Publisher Copyright:
© 2019 Corrales et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/5
Y1 - 2019/5
N2 - Genotype-to-phenotype correlation studies in myotonic dystrophy type 1 (DM1) have been confounded by the age-dependent, tissue-specific and expansion-biased features of somatic mosaicism of the expanded CTG repeat. Previously, we showed that by controlling for the confounding effects of somatic instability to estimate the progenitor allele CTG length in blood DNA, age at onset correlations could be significantly improved. To determine the suitability of saliva DNA as a source for genotyping, we used small pool-PCR to perform a detailed quantitative study of the somatic mutational dynamics of the CTG repeat in saliva and blood DNA from 40 DM1 patients. Notably, the modal allele length in saliva was only moderately higher in saliva and not as large as previously observed in most other tissues. The lower boundary of the allele distribution was also slightly higher in saliva than it was in blood DNA. However, the progenitor allele length estimated in blood explained more of the variation in age at onset than that estimated from saliva. Interestingly, although the modal allele length was slightly higher in saliva, the overall degree of somatic variation was typically lower than in blood DNA, revealing new insights into the tissue-specific dynamics of somatic mosaicism. These data indicate that saliva constitutes an accessible, non-invasive and suitable DNA sample source for performing genetic studies in DM1.
AB - Genotype-to-phenotype correlation studies in myotonic dystrophy type 1 (DM1) have been confounded by the age-dependent, tissue-specific and expansion-biased features of somatic mosaicism of the expanded CTG repeat. Previously, we showed that by controlling for the confounding effects of somatic instability to estimate the progenitor allele CTG length in blood DNA, age at onset correlations could be significantly improved. To determine the suitability of saliva DNA as a source for genotyping, we used small pool-PCR to perform a detailed quantitative study of the somatic mutational dynamics of the CTG repeat in saliva and blood DNA from 40 DM1 patients. Notably, the modal allele length in saliva was only moderately higher in saliva and not as large as previously observed in most other tissues. The lower boundary of the allele distribution was also slightly higher in saliva than it was in blood DNA. However, the progenitor allele length estimated in blood explained more of the variation in age at onset than that estimated from saliva. Interestingly, although the modal allele length was slightly higher in saliva, the overall degree of somatic variation was typically lower than in blood DNA, revealing new insights into the tissue-specific dynamics of somatic mosaicism. These data indicate that saliva constitutes an accessible, non-invasive and suitable DNA sample source for performing genetic studies in DM1.
UR - http://www.scopus.com/inward/record.url?scp=85065563440&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065563440&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0216407
DO - 10.1371/journal.pone.0216407
M3 - Article
C2 - 31048891
AN - SCOPUS:85065563440
SN - 1932-6203
VL - 14
JO - PloS one
JF - PloS one
IS - 5
M1 - e0216407
ER -