OMIA:001918-9615 : Progressive retinal atrophy, type 3, FAM161A-related in Canis lupus familiaris |
Categories: Vision / eye phene
Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 606068 (trait) , 613596 (gene)
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal recessive
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2014
Inheritance: Bjerkas and Narfstrom (1994) reported data supporting autosomal recessive inheritance.
Mapping: From a GWAS conducted on 22 affected and 10 control Tibetan Spaniels, each genotyped with an Illumina SNP20 BeadChip (yielding 15,674 informative SNPs), Downs and Mellersch (2014) mapped this disorder to a 3.8Mb candidate region on chromosome CFA10.
Molecular basis: Encouraged by the fact that a comparative (human) candidate gene (namely FAM161A, mutations in which cause retinosis pigmentosa (RP) 28) shows conserved synteny with the candidate region identified in their GWAS (see Mapping section), Downs and Mellersch (2014) next-gen sequenced the 3.8Mb candidate region in 4 affected, 2 obligate carriers and 2 unaffecteds, identifying the most likely candidate causal variant as a large insertion in the region of exon 5 of FAM161A. Subsequent Sanger-sequencing of this region in 29 affecteds, 10 obligate carriers and 41 unaffecteds identified a ~230bp insertion containing a 132bp short interspersed nuclear element (SINE), near the splice acceptor site of exon 5. As reported by Downs and Mellersch (2014), "Analysis of mRNA from an affected dog revealed that the SINE causes exon skipping, resulting in a frame shift, leading to a downstream premature termination codon and possibly a truncated protein product."
Prevalence: While the FAM161A insertion has strong claims to being causative (see Molecular section), Downs and Mellersch (2014) cautioned that heterogeneity exists: "This [FAM161A] mutation segregates with the disease in 22 out of 35 cases tested (63%). Of the PRA controls, none are homozygous for the mutation, 15% carry the mutation and 85% are homozygous wildtype. This mutation was also identified in Tibetan Terriers, although our results indicate that PRA is genetically heterogeneous in both Tibetan Spaniels and Tibetan Terriers."
Breeds: Tibetan Spaniel, Tibetan Terrier.
Associated gene:
| Symbol | Description | Species | Chr | Location | OMIA gene details page | Other Links |
|---|---|---|---|---|---|---|
| FAM161A | family with sequence similarity 161, member A | Canis lupus familiaris | 10 | NC_006592.2 (64995951..64966161) | FAM161A | Homologene, Ensembl , NCBI gene |
Variants
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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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 925 | Tibetan Spaniel Tibetan Terrier | Progressive retinal atrophy, type 3, FAM161A-related | FAM161A | insertion, gross (>20) | Naturally occurring variant | CanFam3.1 | 10 | g.61822372_61822373insN[(230)] | A ~230bp insertion containing a 132bp short interspersed nuclear element (SINE), near the splice acceptor site of exon 5 CanFam2.0 coordinate published as g.64974130 | 2014 | 24705771 |
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.
| 2016 | Downs, L.M., Aguirre, G.D. : |
| FAM161A and TTC8 are differentially expressed in non-allelelic early onset retinal degeneration. Adv Exp Med Biol 854:201-7, 2016. Pubmed reference: 26427412 . DOI: 10.1007/978-3-319-17121-0_27. | |
| 2014 | Downs, L.M., Mellersh, C.S. : |
| An Intronic SINE Insertion in FAM161A that Causes Exon-Skipping Is Associated with Progressive Retinal Atrophy in Tibetan Spaniels and Tibetan Terriers. PLoS One 9:e93990, 2014. Pubmed reference: 24705771 . DOI: 10.1371/journal.pone.0093990. | |
| 2004 | Ketteritzsch, K., Hamann, H., Brahm, R., Grussendorf, H., Rosenhagen, CU., Distl, O. : |
| Genetic analysis of presumed inherited eye diseases in Tibetan Terriers. Vet J 168:151-9, 2004. Pubmed reference: 15301758 . DOI: 10.1016/S1090-0233(03)00143-6. | |
| 1994 | Bjerkas, E., Narfstrom, K. : |
| Progressive Retinal Atrophy in the Tibetan Spaniel in Norway and Sweden Veterinary Record 134:377-379, 1994. Pubmed reference: 8009801 . | |
| 1988 | Millichamp, N.J., Curtis, R., Barnett, K.C. : |
| Progressive retinal atrophy in Tibetan terriers. J Am Vet Med Assoc 192:769-76, 1988. Pubmed reference: 3356591 . | |
| 1978 | Barnett, K.C., Curtis, R. : |
| Lens luxation and progressive retinal atrophy in the Tibetan Terrier Veterinary Record :160 only, 1978. Pubmed reference: 308725 . |
Edit History
- Created by Frank Nicholas on 09 Apr 2014
- Changed by Frank Nicholas on 09 Apr 2014