Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis

C. S. Mellersh, M. E G Boursnell, L. Pettitt, E. J. Ryder, N. G. Holmes, D. Grafham, O. P. Forman, J. Sampson, K. C. Barnett, Susan H Blanton, M. M. Binns, M. Vaudin

Research output: Contribution to journalArticle

75 Citations (Scopus)

Abstract

Cone-rod dystrophy 1 (cord1) is a recessive condition that occurs naturally in miniature longhaired dachshunds (MLHDs). We mapped the cord1 locus to a region of canine chromosome CFA15 that is syntenic with a region of human chromosome 14 (HSA14q11.2) containing the retinitis pigmentosa GTPase regulator-interacting protein 1 (RPGRIP1) gene. Mutations in RPGRIP1 have been shown to cause Leber congenital amaurosis, a group of retinal dystrophies that represent the most common genetic causes of congenital visual impairment in infants and children. Using the newly available canine genome sequence we sequenced RPGRIP1 in affected and carrier MLHDs and identified a 44-nucleotide insertion in exon 2 that alters the reading frame and introduces a premature stop codon. All affected and carrier dogs within an extended inbred pedigree were homozygous and heterozygous, respectively, for the mutation. We conclude the mutation is responsible for cord1 and demonstrate that this canine disease is a valuable model for exploring disease mechanisms and potential therapies for human Leber congenital amaurosis.

Original languageEnglish
Pages (from-to)293-301
Number of pages9
JournalGenomics
Volume88
Issue number3
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Fingerprint

Leber Congenital Amaurosis
Retinitis Pigmentosa
GTP Phosphohydrolases
Canidae
Mutation
Retinal Dystrophies
Dog Diseases
Chromosomes, Human, Pair 14
Reading Frames
Proteins
Nonsense Codon
Vision Disorders
Human Chromosomes
Pedigree
Exons
Nucleotides
Chromosomes
Genome
Dogs
Cone-Rod Dystrophy 1

Keywords

  • Canine
  • Cone-rod dystrophy
  • Leber congenital amaurosis
  • RPGRIP1

ASJC Scopus subject areas

  • Genetics

Cite this

Mellersh, C. S., Boursnell, M. E. G., Pettitt, L., Ryder, E. J., Holmes, N. G., Grafham, D., ... Vaudin, M. (2006). Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. Genomics, 88(3), 293-301. https://doi.org/10.1016/j.ygeno.2006.05.004

Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. / Mellersh, C. S.; Boursnell, M. E G; Pettitt, L.; Ryder, E. J.; Holmes, N. G.; Grafham, D.; Forman, O. P.; Sampson, J.; Barnett, K. C.; Blanton, Susan H; Binns, M. M.; Vaudin, M.

In: Genomics, Vol. 88, No. 3, 01.09.2006, p. 293-301.

Research output: Contribution to journalArticle

Mellersh, CS, Boursnell, MEG, Pettitt, L, Ryder, EJ, Holmes, NG, Grafham, D, Forman, OP, Sampson, J, Barnett, KC, Blanton, SH, Binns, MM & Vaudin, M 2006, 'Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis', Genomics, vol. 88, no. 3, pp. 293-301. https://doi.org/10.1016/j.ygeno.2006.05.004
Mellersh, C. S. ; Boursnell, M. E G ; Pettitt, L. ; Ryder, E. J. ; Holmes, N. G. ; Grafham, D. ; Forman, O. P. ; Sampson, J. ; Barnett, K. C. ; Blanton, Susan H ; Binns, M. M. ; Vaudin, M. / Canine RPGRIP1 mutation establishes cone-rod dystrophy in miniature longhaired dachshunds as a homologue of human Leber congenital amaurosis. In: Genomics. 2006 ; Vol. 88, No. 3. pp. 293-301.
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