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 |
Journal | Genet Med |
Volume | 22 |
Issue | 11 |
Pagination | 1768-1776 |
Date Published | 2020 Nov |
ISSN | 1530-0366 |
Keywords | Exome, Exome Sequencing, High-Throughput Nucleotide Sequencing, Humans, Mosaicism, Parents |
Abstract | 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. |
DOI | 10.1038/s41436-020-0897-z |
Alternate Journal | Genet Med |
PubMed ID | 32655138 |
PubMed Central ID | PMC7606563 |
Grant List | K08 HG008986 / HG / NHGRI NIH HHS / United States R01 HD087292 / HD / NICHD NIH HHS / United States UM1 HG006542 / HG / NHGRI NIH HHS / United States |
Low-level parental somatic mosaic SNVs in exomes from a large cohort of trios with diverse suspected Mendelian conditions.
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