Low-level parental somatic mosaic SNVs in exomes from a large cohort of trios with diverse suspected Mendelian conditions
Authors:
- Tomasz Gambin,
- Qian Liu,
- Justyna Karolak,
- Christopher M. Grochowski,
- Nina G. Xie,
- Tzong-Lin Wu,
- Yan Helen Yan,
- Ye Cao,
- Zeynep H. Coban Akdemir,
- Theresa A. Wilson,
- Shalini N. Jhangiani,
- Ed Chen,
- Christine M. Eng,
- Donna Muzny,
- Jennifer E. Posey,
- Y. Yang,
- Dan Zhang,
- Chad Shaw,
- Pengfei Liu,
- James R. Lupski,
- P. Stankiewicz
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 <1%) level mosaic. Detection precision in parental samples with two or more alternate reads was 63.6% (BHCMG) and 43.6% (BG). In nine investigated individuals, we observed variability of mosaic ratios among blood, saliva, fibroblast, buccal, hair, and urine samples. 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.
- Record ID
- WUT794f43c31b594548a9b589249029563f
- Author
- Journal series
- Genetics in Medicine, ISSN 1098-3600, e-ISSN 1530-0366
- Issue year
- 2020
- Pages
- 1-9
- Publication size in sheets
- 0.50
- ASJC Classification
- DOI
- DOI:10.1038/s41436-020-0897-z Opening in a new tab
- Language
- (en) English
- Score (nominal)
- 200
- Score source
- journalList
- Score
- = 200.0, 08-05-2022, ArticleFromJournal
- Publication indicators
- = 2; = 11; : 2018 = 3.488; : 2020 (2 years) = 8.822 - 2020 (5 years) =12.372
- Citation count
- 16
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- Uniform Resource Identifier
- https://repo.pw.edu.pl/info/article/WUT794f43c31b594548a9b589249029563f/
- URN
urn:pw-repo:WUT794f43c31b594548a9b589249029563f
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or PerishOpening in a new tab system.