OMIA 001918-9615 : Progressive retinal atrophy, type 3, FAM161A-related in Canis lupus familiaris

Possibly relevant human trait(s) and/or gene(s) (MIM number): 606068

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

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.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Tibetan spaniel Tibetan Terrier Progressive retinal atrophy, type 3, FAM161A-related FAM161A insertion, gross (>20) CanFam2.0 10 g.64974130 A ~230bp insertion containing a 132bp short interspersed nuclear element (SINE), near the splice acceptor site of exon 5 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