OMIA:002112-9615 : Osteogenesis imperfecta, COL1A2-related in Canis lupus familiaris
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
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."
Breeds: Beagle, Chow Chow.
|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|
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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|
|762||Beagle||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||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||Osteogenesis imperfecta, COL1A2-related||COL1A2||splicing||Naturally occurring variant||CanFam3.1||14||g.19898487G>A||c.936+1G>A||2018||29036614|
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.|
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