OMIA 002127-9913 : Osteogenesis imperfecta, type II, COL1A1-related in Bos taurus

Possibly relevant human trait(s) and/or gene(s) (MIM number): 166210

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 the indel 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."

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."

Breeds: Fleckvieh, Red Angus.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
COL1A1 collagen type I alpha 1 Bos taurus 19 NC_037346.1 (36457701..36475647) COL1A1 Homologene, Ensembl, NCBI gene

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Red Angus Osteogenesis imperfecta, type II, COL1A1-related COL1A1 missense ARS-UCD1.2 19 g.36463798G>A c.1063G>A p.Gly355Ser 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.) ss1342331437356 2019 30788588
Fleckvieh Osteogenesis imperfecta, type II, COL1A1-related COL1A1 indel, small (<=20) UMD3.1 19 g.37101299_37101302delinsT p.A1049_P1050DelInsS 2017 28904385

References


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.
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., 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.

Edit History


  • Created by Frank Nicholas on 18 Sep 2017
  • Changed by Frank Nicholas on 18 Sep 2017
  • Changed by Frank Nicholas on 19 Sep 2017
  • Changed by Frank Nicholas on 26 Feb 2019
  • Changed by Frank Nicholas on 21 Sep 2019