OMIA:002132-9615 : Lethality, BTBD17-related in Canis lupus familiaris
Categories: Mortality / aging (incl. embryonic lethal)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive lethal
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2017
Cross-species summary: Renamed, previously listed as 'Abortion (embryonic lethality), BTBD17-related' [12/06/2023]
Species-specific description: See also 'OMIA:000901-9615 : XX testicular DSD (Disorder of Sexual Development) in Canis lupus familiaris' for the association of the BTBD17 variant with differences in sexual development (DSD)
Inheritance: Meyers-Wallen et al. (2017): "Because genotyping results at the 6048201 locus indicated that the G+G+ [homozygous for the G insertion] genotype was uncommon in XX DSD purebred pet dogs (3% G+G+, . . . ), but common in mixed breed XX DSD in the model pedigree (83% G+G+, . . . ), we hypothesized this genotype was deleterious in purebred dogs. Therefore, we genotyped pedigrees from purebred and crossbred breeding experiments in which the probability of G+G+ offspring varied from 0.25–0.5 . . . . All offspring were born alive and birth weights within the same litter were similar. None of the offspring were G+G+ genotype, including crossbred offspring sired by males from the model pedigree that had previously produced G+G+ and G+/- XX DSD offspring (sires C734 and C752, . . . ). These results indicated that embryonic lethality was associated with the G+G+ genotype in the GSHP genetic background."
Molecular basis: Meyers-Wallen et al. (2017) reported that the homozygous genotype for a variant in intron 1 of the BTBD17 gene ("a guanine insertion (G+) at CFA9: 6048201–6048202 . . . , rs852549625)") is associated with embryonic lethality in dogs with German shorthair pointer background.
Meadows et al. (2023) investigated the presence of 463 likely causal variants in whole genome sequencing data of dogs in the Dog10K collection and identified that the BTBD17 variant reported by Meyers-Wallen et al. (2017) was homozygous in 179 dogs and heterozygous in 407 dogs from various breeds, while 1172 dogs were homozygous for the wildtype allele. The variant is therefore unlikely to be causal, and the association with homozygous lethality may be specific to German Shorthaired Pointers.
Breed: German Shorthaired Pointer.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|BTBD17||BTB (POZ) domain containing 17||Canis lupus familiaris||9||NC_051813.1 (6719394..6725404)||BTBD17||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|851||German Shorthaired Pointer||Abortion (embryonic lethality), BTBD17-related||BTBD17||insertion, small (<=20)||Naturally occurring variant||CanFam3.1||9||g.6048201_6048202insG||c.85+206_85+207insG||ROS_Cfam_1.0:g.6720627_6720628insG ENSCAFT00845033049.1:c.85+206_85+207insG; the homozygous variant genotype is associated with embryonic lethality in German Shorthaired Pointer, but may not be causal as the variant was observed at a high frequency in both heterozygous and homozygous form across normal dogs from multiple breeds (PMID:37582787)||rs852549625||2017||29053721|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2023||Meadows, J.R.S., Kidd, J.M., Wang, G.D., Parker, H.G., Schall, P.Z., Bianchi, M., Christmas, M.J., Bougiouri, K., Buckley, R.M., Hitte, C., Nguyen, A.K., Wang, C., Jagannathan, V., Niskanen, J.E., Frantz, L.A.F., Arumilli, M., Hundi, S., Lindblad-Toh, K., Ginja, C., Agustina, K.K., André, C., Boyko, A.R., Davis, B.W., Drögemüller, M., Feng, X.Y., Gkagkavouzis, K., Iliopoulos, G., Harris, A.C., Hytönen, M.K., Kalthoff, D.C., Liu, Y.H., Lymberakis, P., Poulakakis, N., Pires, A.E., Racimo, F., Ramos-Almodovar, F., Savolainen, P., Venetsani, S., Tammen, I., Triantafyllidis, A., vonHoldt, B., Wayne, R.K., Larson, G., Nicholas, F.W., Lohi, H., Leeb, T., Zhang, Y.P., Ostrander, E.A. :|
|Genome sequencing of 2000 canids by the Dog10K consortium advances the understanding of demography, genome function and architecture. Genome Biol 24:187, 2023. Pubmed reference: 37582787 . DOI: 10.1186/s13059-023-03023-7.|
|2017||Meyers-Wallen, V.N., Boyko, A.R., Danko, C.G., Grenier, J.K., Mezey, J.G., Hayward, J.J., Shannon, L.M., Gao, C., Shafquat, A., Rice, E.J., Pujar, S., Eggers, S., Ohnesorg, T., Sinclair, A.H. :|
|XX Disorder of Sex Development is associated with an insertion on chromosome 9 and downregulation of RSPO1 in dogs (Canis lupus familiaris). PLoS One 12:e0186331, 2017. Pubmed reference: 29053721 . DOI: 10.1371/journal.pone.0186331.|
- Created by Frank Nicholas on 24 Oct 2017
- Changed by Imke Tammen2 on 12 Jun 2023
- Changed by Imke Tammen2 on 18 Aug 2023