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Canine reference genome accuracy impacts variant calling: Lessons learned from investigating embryonic lethal
Nathan A Kinsey1, Janelle M Belanger1,
1Department of Animal Science, University of California, Davis, USA.
Animal Genetics
|December 26, 2022
Summary
Investigating embryonic lethal variants in 675 canids revealed most were sequencing artifacts. Using updated reference genomes improves accuracy for identifying true genetic variants in canine populations.
Area of Science:
- Genomics
- Canine Genetics
- Population Genetics
Background:
- Embryonic lethal variants can be identified by their absence in homozygous states within a population.
- Whole genome sequencing is a powerful tool for variant discovery.
Purpose of the Study:
- To identify potentially embryonic lethal variants in canids using whole genome sequence data.
- To assess the accuracy of variant calling using the CanFam3.1 reference genome.
Main Methods:
- Analysis of whole genome sequence data from 675 canids.
- Identification of variants with missing homozygosity and high predicted impact.
- Scrutiny of sequence reads to differentiate true variants from artifacts.
- Comparison of variant calling using different canine reference genomes.
Main Results:
- 45 variants in 32 genes were initially identified as potentially lethal.
- Subsequent analysis revealed that 44 of these variants were artifacts of the variant calling process.
- The CanFam3.1 reference genome contributed significantly to these false positives.
- A single potentially lethal variant was confirmed.
Conclusions:
- The widely used CanFam3.1 reference genome can lead to significant artifacts in variant calling.
- Utilizing multiple and newer reference genomes is crucial for accurate variant identification in canids.
- This highlights the importance of careful validation in genetic studies to avoid erroneous conclusions about variant lethality.
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