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Why is mosaic variation difficult to identify?
Sequence reads
AA A A A A
Allele ratio = 8% Noise or mosaicism?
Allele ratio = 38% Heterozygous or mosaicism?
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Sequence reads
Low‐level mosacisms are difficult to distinguish from homozygous reference
High‐level mosaicisms are difficult to distinguish from heterozygous variants
Germline mutations
Somatic mutations
1. Determine allele ratio for true heterozygous mutations using inherited variants
2. Compare allelic ratios of de novo mutations to true heterozygous variant distribution
3. Identify de novo variations with allele ratios outside expected distribution and follow up using targeted re‐sequencing
4 of 4,081 DNMs ~0.1%
Somatic
Germline
7 of 127 DNMs ~6.5%
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