biostudies-literatureKinsey NAJane ja Aatos Erkon SäätiöAlbert-Heim-StiftungNIH Office of the DirectorMater FoundationNIH HHS706-708https://www.ebi.ac.uk/biostudies/studies/S-EPMC9784012biostudies-literatureUnknown53(5)Deficient homozygosity of a variant maintained in a population suggests that the variant may be embryonic lethal. We examined whole genome sequence data from 675 canids to investigate for variants with missing homozygosity and high predicted impact. Our analysis identified 45 variants, in 32 genes. However, further scrutiny of the sequence reads revealed that all but one of these variants were artifacts of the variant calling process when using CanFam3.1, a widely utilized canine reference genome. We demonstrate that the use of multiple, newer reference genomes could reduce artifacts and lead to more accurate variant identification.Animal geneticsCanine reference genome accuracy impacts variant calling: Lessons learned from investigating embryonic lethal variants.PMC9784012K01 OD027051105K01‐OD019912K01‐OD027051Belanger JMDog Biomedical Variant Database ConsortiumOberbauer AMKinsey NAfalseCanine reference genome accuracy impacts variant calling: Lessons learned from investigating embryonic lethal variants.Deficient homozygosity of a variant maintained in a population suggests that the variant may be embryonic lethal. We examined whole genome sequence data from 675 canids to investigate for variants with missing homozygosity and high predicted impact. Our analysis identified 45 variants, in 32 genes. However, further scrutiny of the sequence reads revealed that all but one of these variants were artifacts of the variant calling process when using CanFam3.1, a widely utilized canine reference genome. We demonstrate that the use of multiple, newer reference genomes could reduce artifacts and lead to more accurate variant identification.2022-01-01T00:00:00Z2022 Oct2025-04-05T09:42:36.678Z2025-04-05T09:42:36.678ZS-EPMC97840123656946010.1111/age.13241