Insights Into de novo Mutation Variation in Lithuanian Exome

Frontiers in Genetics
Laura PranckėnienėVaidutis Kučinskas

Abstract

In the last decade, one of the biggest challenges in genomics research has been to distinguish definitive pathogenic variants from all likely pathogenic variants identified by next-generation sequencing. This task is particularly complex because of our lack of knowledge regarding overall genome variation and pathogenicity of the variants. Therefore, obtaining sufficient information about genome variants in the general population is necessary as such data could be used for the interpretation of de novo mutations (DNMs) in the context of patient's phenotype in cases of sporadic genetic disease. In this study, data from whole-exome sequencing of the general population in Lithuania were directly examined. In total, 84 (VarScan) and 95 (VarSeqTM) DNMs were identified and validated using different algorithms. Thirty-nine of these mutations were considered likely to be pathogenic based on gene function, evolutionary conservation, and mutation impact. The mutation rate estimated per position pair per generation was 2.74 × 10-8 [95% CI: 2.24 × 10-8-3.35 × 10-8] (VarScan) and 2.4 × 10-8 [95% CI: 1.96 × 10-8-2.99 × 10-8] (VarSeqTM), with 1.77 × 10-8 [95% CI: 6.03 × 10-9-5.2 × 10-8] de novo indels per position per generation. The rate of g...Continue Reading

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Citations

Oct 20, 2019·Molecular Genetics & Genomic Medicine·Laura PranckėnienėVaidutis Kučinskas

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Datasets Mentioned

BETA
GM12878
PRJEB25864

Methods Mentioned

BETA
5500 sequencing
deamination

Software Mentioned

SAMtools
SnpSift
GATK UnifiedGenotyper
FATHMM Taster
VarSeq TM
Lifescope
HaplotypeCaller
VarScan
Integrative Genomics Viewer
ANNOVAR

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