|Title||Low-level parental somatic mosaic SNVs in exomes from a large cohort of trios with diverse suspected Mendelian conditions.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Gambin, T, Liu, Q, Karolak, JA, Grochowski, CM, Xie, NG, Wu, LR, Yan, YHelen, Cao, Y, Akdemir, ZHCoban, Wilson, TA, Jhangiani, SN, Chen, E, Eng, CM, Muzny, DM, Posey, JE, Yang, Y, Zhang, DY, Shaw, C, Liu, P, Lupski, JR, Stankiewicz, P|
|Date Published||2020 Jul 13|
PURPOSE: The goal of this study was to assess the scale of low-level parental mosaicism in exome sequencing (ES) databases.
METHODS: We analyzed approximately 2000 family trio ES data sets from the Baylor-Hopkins Center for Mendelian Genomics (BHCMG) and Baylor Genetics (BG). Among apparent de novo single-nucleotide variants identified in the affected probands, we selected rare unique variants with variant allele fraction (VAF) between 30% and 70% in the probands and lower than 10% in one of the parents.
RESULTS: Of 102 candidate mosaic variants validated using amplicon-based next-generation sequencing, droplet digital polymerase chain reaction, or blocker displacement amplification, 27 (26.4%) were confirmed to be low- (VAF between 1% and 10%) or very low (VAF
CONCLUSION: Our computational pipeline enables robust discrimination between true and false positive candidate mosaic variants and efficient detection of low-level mosaicism in ES samples. We confirm that the presence of two or more alternate reads in the parental sample is a reliable predictor of low-level parental somatic mosaicism.
|Alternate Journal||Genet. Med.|