OMIA:001918-9615 : Retinal atrophy, progressive, FAM161A-related in Canis lupus familiaris (dog)

Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 606068 (trait) , 613596 (gene)

Links to relevant human diseases in MONDO:

Single-gene trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: yes

Year key variant first reported: 2014

Cross-species summary: Renamed from "Retinal atrophy, progressive, type 3, FAM161A-related" to "Retinal atrophy, progressive, FAM161A-related" [01/082024]

Species-specific name: Progressive retinal atrophy 3, PRA3 (Tibetan Terrier); Progressive retinal atrophy 6, PRA6 (English Shepherd)

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."
Stanbury et al. (2024) investigated English Shepherds which "were diagnosed with PRA at approximately 5 years old and tested clear of all published PRA genetic variants. ... [The authors] utilised a combined approach of whole genome sequencing of the probands and homozygosity mapping of four cases and 22 controls and identified a short interspersed nuclear element within an alternatively spliced exon in FAM161A. The XP_005626197.1 c.17929_ins210 variant was homozygous in six PRA cases and heterozygous or absent in control dogs, consistent with a recessive mode of inheritance. The insertion is predicted to extend exon 4 by 39 aberrant amino acids followed by an early termination stop codon."

Prevalence: While the FAM161A insertion reporteed by Downs and Mellersch (2014) has strong claims to being causative (see Molecular section), the authors cautioned that heterogeneity exists: "This [FAM161A, omia.variant:925] 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: English Shepherd (Dog) (VBO_0200496), Tibetan Spaniel (Dog) (VBO_0201352), Tibetan Terrier (Dog) (VBO_0201353).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

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

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 Year Published PubMed ID(s) Acknowledgements
925 Tibetan Spaniel (Dog) Tibetan Terrier (Dog) Retinal atrophy, progressive, type 3, FAM161A-related FAM161A PRA3 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
1706 English Shepherd (Dog) Retinal atrophy, progressive, type 6, FAM161A-related FAM161A PRA6 insertion, gross (>20) Naturally occurring variant UU_Cfam_GSD_1.0 10 NC_049231.1:g.63116065_63116066ins[N[210];63116051_63116065] XM_038551371.1:c.1728_1729ins[N[210];1714-1728] XP_038407299.1:p.(Q576_M577ins*50)) published as XP_005626197.1 c.17929_ins210 2024 39062732

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001918-9615: 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.

2024 Stanbury, K., Schofield, E.C., McLaughlin, B., Forman, O.P., Mellersh, C.S. :
Exonic short interspersed nuclear element insertion in FAM161A is associated with autosomal recessive progressive retinal atrophy in the English Shepherd. Genes (Basel) 15:952, 2024. Pubmed reference: 39062732. DOI: 10.3390/genes15070952.
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. Vet Rec 134:377-9, 1994. Pubmed reference: 8009801. DOI: 10.1136/vr.134.15.377.
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 Vet Rec 103:160, 1978. Pubmed reference: 308725. DOI: 10.1136/vr.103.8.160.

Edit History


  • Created by Frank Nicholas on 09 Apr 2014
  • Changed by Frank Nicholas on 09 Apr 2014
  • Changed by Imke Tammen2 on 28 Jul 2024
  • Changed by Imke Tammen2 on 01 Aug 2024
  • Changed by Imke Tammen2 on 06 Sep 2024