OMIA:002112-9615 : Osteogenesis imperfecta, COL1A2-related in Canis lupus familiaris (dog)

Categories: Skeleton phene (incl. short stature & teeth)

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 166210 (trait) , 259420 (trait) , 166220 (trait) , 120160 (gene)

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: 2001

Cross-species summary: Abnormally brittle bones that fracture easily due to variants in the COL1A2 gene.

Species-specific symbol: OI

Molecular basis: Campbell et al. (2001) reported a likely causal variant in an affected Beagle as: "a mutation in which nucleotides 3991-3994 ("CTAG") were replaced with "TGTCATTGG." The first seven bases of the inserted sequence were identical to nucleotides 4002-4008 of the normal canine COL1A2 sequence. The resulting frameshift changed 30 amino acids and introduced a premature stop codon." In an affected Chow Chow, Quist et al. (2017) identified a likely causal variant as "a G>A heterozygous mutation in the splice donor site of exon 18 of the COL1A2 gene (c.936+1G>A). The splice donor mutation was not detected among 91 control dogs representing 21 breeds. A comparative analysis of exon 18 and the exon-intron junction further showed that the mutated splice donor site is conserved among vertebrates." Letko et al. (2019) reported a "de novo in‐frame duplication in the COL1A2 gene [g.19898279_19898281dup; c.877_879dupCCC] in a Lagotto Romagnolo dog with osteogenesis imperfecta". The de novo nature of the variant was concluded from the observation that "both parents, as well as all four littermates, were homozygous wild type . . . . An additional 87 unrelated Lagotto Romagnolo dogs were genotyped homozygous wild type, which confirmed the presence of variant allele only in the single affected dog."

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Breeds: Beagle (Dog) (VBO_0200131), Chow Chow (Dog) (VBO_0200361), Lagotto Romagnolo (Dog) (VBO_0200804).
Breeds in which the phene has been documented. For breeds in which a likely causal variant has been documented, see the variant table below

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
COL1A2 collagen, type I, alpha 2 Canis lupus familiaris 14 NC_051818.1 (19699099..19734901) COL1A2 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.

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
762 Beagle (Dog) Osteogenesis imperfecta, COL1A2-related COL1A2 delins, small (<=20) Naturally occurring variant CanFam3.1 14 g.(19918265_19918268delinsTGTCATTGG) c.3656_3859delinsTGTCATTGG p.(L1286Cfs*31) NM_001003187.1; NP_001003187.1; "a mutation in which nucleotides 3991-3994 ("CTAG") were replaced with "TGTCATTGG." The first seven bases of the inserted sequence were identical to nucleotides 4002-4008 of the normal canine COL1A2 sequence. The resulting frameshift changed 30 amino acids and introduced a premature stop codon." The genomic information is presented in brackets as the variant was detected in cDNA and the genomic position is predicted. Coordinates in the table have been updated to a recent reference genome and or transcripts. 2001 11393792
1114 Lagotto Romagnolo (Dog) Osteogenesis imperfecta, COL1A2-related COL1A2 duplication Naturally occurring variant CanFam3.1 14 g.19898279_19898281dup c.877_879dup p.(P293dup) NM_001003187.1; NP_001003187.1 2019 31468557
852 Chow Chow (Dog) Osteogenesis imperfecta, COL1A2-related COL1A2 splicing Naturally occurring variant CanFam3.1 14 g.19898487G>A c.936+1G>A 2018 29036614

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002112-9615: Online Mendelian Inheritance in Animals (OMIA) [dataset]. https://omia.org/. https://doi.org/10.25910/2AMR-PV70

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 Letko, A., Zdora, I., Hitzler, V., Jagannathan, V., Beineke, A., Möhrke, C., Drögemüller, C., Letko, A., Zdora, I., Hitzler, V., Jagannathan, V., Beineke, A., Möhrke, C., Drögemüller, C. :
A de novo in-frame duplication in the COL1A2 gene in a Lagotto Romagnolo dog with osteogenesis imperfecta. Anim Genet , 2019. Pubmed reference: 31468557. DOI: 10.1111/age.12843.
2018 Quist, E.M., Doan, R., Pool, R.R., Porter, B.F., Bannasch, D.L., Dindot, S.V. :
Identification of a candidate mutation in the COL1A2 gene of a Chow Chow with osteogenesis imperfecta. J Hered 109:308-314, 2018. Pubmed reference: 29036614. DOI: 10.1093/jhered/esx074.
2001 Campbell, B.G., Wootton, J.A.M., Macleod, J.N., Minor, R.R. :
Canine COL1A2 mutation resulting in C-terminal truncation of pro-alpha 2(I) and severe osteogenesis imperfecta Journal of Bone & Mineral Research 16:1147-1153, 2001. Pubmed reference: 11393792. DOI: 10.1359/jbmr.2001.16.6.1147.

Edit History


  • Created by Frank Nicholas on 13 Jul 2017
  • Changed by Frank Nicholas on 13 Jul 2017
  • Changed by Frank Nicholas on 25 Oct 2017
  • Changed by Frank Nicholas on 23 Jan 2018
  • Changed by Frank Nicholas on 18 Sep 2019
  • Changed by Imke Tammen2 on 05 Jun 2023