OMIA:002208-9615 : Eye malformation, SIX6-related in Canis lupus familiaris
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 212550 (trait) , 606326 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant with incomplete penetrance
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2019
Species-specific name: Congenital eye malformation
Inheritance: Hug et al. (2019): "All cases traced back to the same male ancestor, but had quite diverse maternal lineages . . . . Seven out of 28 recorded puppies were affected and males and females were affected in equal proportions. As we could not identify any common ancestors in the maternal lines of the cases, we hypothesized an autosomal dominant inheritance with incomplete penetrance as the most likely mode of inheritance."
Molecular basis: By comparing the genome sequence of one affected Golden Retriever with the sequence of 601 control genomes, Hug et al. (2019) identified a "heterozygous private nonsense variant, c.487C>T . . . in the SIX6 gene. This variant is predicted to truncate about a third of the open reading frame, p.(Gln163*) . . . We hypothesize that the residual amount of functional SIX6 protein likely to be expressed in heterozygous dogs is sufficient to explain the observed incomplete penetrance and the varying severity of the eye defects in the affected dogs."
Prevalence: Hug et al. (2019): "All three available cases were heterozygous. Five additional close relatives including the common sire were also heterozygous, but did not show any obvious eye phenotypes. The variant was absent from the 464 unrelated Golden Retrievers and 17 non-affected siblings of the cases."
Breed: Golden Retriever.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|SIX6||SIX homeobox 6||Canis lupus familiaris||8||NC_051812.1 (35799002..35801808)||SIX6||Homologene, Ensembl , NCBI gene|
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
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|
|1098||Golden Retriever||Eye malformation, congenital||SIX6||nonsense (stop-gain)||Naturally occurring variant||CanFam3.1||8||g.35566504C>T||c.487C>T||p.(Q163*)||XM_547840.6:c.487C>T; XP_547840.3:p.(Gln163*)||2019||31207931|
|2019||Hug, P., Anderegg, L., Dürig, N., Lepori, V., Jagannathan, V., Spiess, B., Richter, M., Leeb, T., Hug, P., Anderegg, L., Dürig, N., Lepori, V., Jagannathan, V., Spiess, B., Richter, M., Leeb, T. :|
|A SIX6 nonsense variant in Golden Retrievers with congenital eye malformations. Genes (Basel) 10:, 2019. Pubmed reference: 31207931 . DOI: 10.3390/genes10060454.|
- Created by Frank Nicholas on 12 Sep 2019
- Changed by Frank Nicholas on 12 Sep 2019
- Changed by Imke Tammen2 on 30 Sep 2021