OMIA:002162-9940 : Hypophosphatasia in Ovis aries (sheep)
In other species: dog
Categories: Skeleton phene (incl. short stature & teeth)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2018
Species-specific description: This ovine disorder has been created by CRISPR/Cas9 technology. This entry is thus describing a genetically-modified organism (GMO).
History: Williams et al. (2018) used "CRISPR/Cas9 to introduce a single point mutation in the tissue nonspecific alkaline phosphatase (TNSALP) gene (ALPL) (1077 C > G) in sheep", to produce a large-animal model of hypophosphatasia (HPP).
Mohamed et al. (2022): "A longitudinal study on dentoalveolar effects of HPP was performed in [genome-edited] sheep using a multimodal approach including computed tomography (CT), high-resolution micro-computed tomography (μCT), and histology."
Clinical features: Mohamed et al. (2022): "Compared to wild-type (WT), compound heterozygous (cHet) sheep with one null allele and the other with the targeted mutant allele exhibited the most severe alveolar bone, acellular cementum, and dentin hypomineralization defects. Sheep homozygous for the mutant allele (Hom) showed alveolar bone and hypomineralization effects and trends in dentin and cementum, whereas sheep heterozygous (Het) for the mutation did not exhibit significant effects."
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|ALPL||alkaline phosphatase, liver/bone/kidney||Ovis aries||2||NC_056055.1 (244983368..244918595)||ALPL||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|
|1486||Hypophosphatasia||ALPL||missense||Genome-editing (CRISPR-Cas9)||Oar_rambouillet_v1.0||2||g.260716094G>C||c.1077C>G||p.(I359M)||XM_027965561.1; XP_027821362.1||2018||30446691|
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.
|2022||Mohamed, F.F., Chavez, M.B., Huggins, S., Bertels, J., Falck, A., Suva, L.J., Foster, B.L., Gaddy, D. :|
|Dentoalveolar defects of hypophosphatasia are recapitulated in a sheep knock-in model. J Bone Miner Res 37:2005-2017, 2022. Pubmed reference: 36053890 . DOI: 10.1002/jbmr.4666.|
|2018||Williams, D.K., Pinzón, C., Huggins, S., Pryor, J.H., Falck, A., Herman, F., Oldeschulte, J., Chavez, M.B., Foster, B.L., White, S.H., Westhusin, M.E., Suva, L.J., Long, C.R., Gaddy, D. :|
|Genetic engineering a large animal model of human hypophosphatasia in sheep. Sci Rep 8:16945, 2018. Pubmed reference: 30446691 . DOI: 10.1038/s41598-018-35079-y.|
- Created by Frank Nicholas on 20 Nov 2019
- Changed by Imke Tammen2 on 11 Sep 2022