OMIA:002127-9913 : Osteogenesis imperfecta, type II, COL1A1-related in Bos taurus (taurine cattle)
Categories: Skeleton phene (incl. short stature & teeth)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2017
Molecular basis: Bourneuf et al. (2017): a de novo likely causal variant is COL1A1 p.1049_1050delinsS in Fleckvieh
Petersen et al. (2019): "Whole-genome sequencing revealed the presence of a missense mutation in the alpha 1 chain of collagen Type I (COL1A1), for which both calves were heterozygous. The variant resulted in the substitution of a glycine residue with serine in the triple helical domain of the protein; in this region, glycine normally occupies every third position as is critical for correct formation of the Type I collagen molecule. Allele-specific amplification by droplet digital PCR further quantified the variant at a frequency of nearly 4.4% in the semen of the sire while it was absent in his blood, supporting the hypothesis of a de novo causative variant for which the germ line of the sire was mosaic."
Jacinto et al. (2021): "Genetic analysis ["an OI type II-affected neonatal Holstein calf"] revealed a private heterozygous missense variant in COL1A1 (c.3917T>A) located in the fibrillar collagen NC1 domain (p.Val1306Glu) that most likely occurred de novo. This confirmed the diagnosis of OI type II and represents the first report of a pathogenic variant in the fibrillar collagen NC domain of COL1A1 associated to OI type II in domestic animals."
Clinical features: Petersen et al. (2019): "Two Red Angus calves by the same sire presented with severe bone and dental fragility, blue sclera, and evidence of in utero fractures consistent with OI congenita. Comparative analyses with human cases suggested the OI in these calves most closely resembled that classified as OI Type II."
Pathology: Petersen et al. (2019): "Microscopically, osteopenia was observed at the distal femoral metaphysis. Trabeculae of primary spongiosa were thin, delicate, and covered by very narrow seams of osteoid. The remodeling was delayed with primary spongiosia extending deeper into the cortex than normal. Microfractures were noted at the juncture between primary and secondary spongiosa in the proximal femoral sample from the bull calf. The osteoid lamella of the femoral cortices was thin and the periosteum was thickened. Dentin and enamel appeared thin."
Holstein (black and white) (Cattle) (VBO_0000237),
Red Angus (Cattle) (VBO_0000350),
Simmental (Cattle) (VBO_0000380).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|COL1A1||collagen type I alpha 1||Bos taurus||19||NC_037346.1 (36457711..36474476)||COL1A1||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|
|1031||Red Angus (Cattle)||Osteogenesis imperfecta, type II, COL1A1-related||COL1A1||missense||Naturally occurring variant||ARS-UCD1.2||19||g.36463798G>A||c.1063G>A||p.(G355S)||Petersen et al. (2019): "PolyPhen-2 predicted the mutation to be “probably damaging” with a score of 1.000 (sensitivity 0.00; specificity 1.00). Similarly, PROVEAN prediction classified the variant as “Deleterious” with a score of − 4.615, exceeding both the default (− 2.5) and stringent (− 4.1) thresholds for this classification." The genomic coordinate in the UMD3.1 assembly is g.37094333G>A (Petersen et al., 2019). The coding sequence coordinates are c.1063G>A (ENSBTAT00000017420.4) (Petersen, pers. comm.)||rs3423092630||rs3423092630||2019||30788588|
|839||Simmental (Cattle)||Osteogenesis imperfecta, type II, COL1A1-related||COL1A1||delins, small (<=20)||Naturally occurring variant||ARS-UCD1.2||19||g.36470764_36470767delinsT||c.3145_3148delinsT||p.(A1049_P1050delinsS)||UMD3.1 position is g.37101299_37101302delinsT; cDNA position based on ENSBTAT00000017420.4||rs876049195||rs876049195||2017||28904385||The genomic location on ARS-UCD1.2 was determined by Katie Eager and Shernae Woolley, EMAI, NSW. Department of Primary Industries.|
|1289||Holstein (black and white) (Cattle)||Osteogenesis imperfecta, type II, COL1A1-related||COL1A1||missense||Naturally occurring variant||ARS-UCD1.2||19||g.36473359T>A||c.3917T>A||p.(V1306E)||NM_001034039.2: c.3917T>A; XP_024835395.1: p.Val1306Glu (Jacinto et al., 2021)||2021||33672767|
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.
|2021||Jacinto et al., Jacinto, J.G.P., Häfliger, I.M., McEvoy, F.J., Drögemüller, C., Agerholm, J.S. :|
|A De Novo Mutation in <i>COL1A1</i> in a Holstein Calf with Osteogenesis Imperfecta Type II. Animals (Basel) 11:561, 2021. Pubmed reference: 33672767 . DOI: 10.3390/ani11020561.|
|2019||Petersen, J.L., Tietze, S.M., Burrack, R.M., Steffen, D.J., Petersen, J.L., Tietze, S.M., Burrack, R.M., Steffen, D.J. :|
|Evidence for a de novo, dominant germ-line mutation causative of osteogenesis imperfecta in two Red Angus calves. Mamm Genome 30:81-87, 2019. Pubmed reference: 30788588 . DOI: 10.1007/s00335-019-09794-4.|
|2017||Bourneuf, E., Otz, P., Pausch, H., Jagannathan, V., Michot, P., Grohs, C., Piton, G., Ammermüller, S., Deloche, M.C., Fritz, S., Leclerc, H., Péchoux, C., Boukadiri, A., Hozé, C., Saintilan, R., Créchet, F., Mosca, M., Segelke, D., Guillaume, F., Bouet, S., Baur, A., Vasilescu, A., Genestout, L., Thomas, A., Allais-Bonnet, A., Rocha, D., Colle, M.A., Klopp, C., Esquerré, D., Wurmser, C., Flisikowski, K., Schwarzenbacher, H., Burgstaller, J., Brügmann, M., Dietschi, E., Rudolph, N., Freick, M., Barbey, S., Fayolle, G., Danchin-Burge, C., Schibler, L., Bed'Hom, B., Hayes, B.J., Daetwyler, H.D., Fries, R., Boichard, D., Pin, D., Drögemüller, C., Capitan, A. :|
|Rapid discovery of de novo deleterious mutations in cattle enhances the value of livestock as model species. Sci Rep 7:11466, 2017. Pubmed reference: 28904385 . DOI: 10.1038/s41598-017-11523-3.|
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