April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Null Mutation in the Chicken Mpdz/mupp1 Gene Causes Retinal Dysplasia and Degeneration: A New Candidate Gene for Human Retinitis Pigmentosa
Author Affiliations & Notes
  • M. Ali
    Ophthalmology & Neuroscience, University of Leeds, Leeds, United Kingdom
  • P. M. Hocking
    The Roslin Institute and Royal School of Veterinary Studies, Edinburgh, United Kingdom
  • S. Finnegan
    Queen's University, Belfast, United Kingdom
  • M. McKibbin
    St. James's University Hospital, Leeds, United Kingdom
  • K. Prescott
    Chapel Allerton Hospital, Leeds, United Kingdom
  • D. McKeegan
    University of Glasgow, Glasgow, United Kingdom
  • D. H. Lester
    University of Abertay, Dundee, United Kingdom
  • D. W. Burt
    The Roslin Institute and Royal School of Veterinary Studies, Edinburgh, United Kingdom
  • W. J. Curry
    Queen's University, Belfast, United Kingdom
  • C. F. Inglehearn
    Ophthalmology & Neuroscience, University of Leeds, Leeds, United Kingdom
  • Footnotes
    Commercial Relationships  M. Ali, None; P.M. Hocking, None; S. Finnegan, None; M. McKibbin, None; K. Prescott, None; D. McKeegan, None; D.H. Lester, None; D.W. Burt, None; W.J. Curry, None; C.F. Inglehearn, None.
  • Footnotes
    Support  MRC Grant G0501050
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 6352. doi:
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      M. Ali, P. M. Hocking, S. Finnegan, M. McKibbin, K. Prescott, D. McKeegan, D. H. Lester, D. W. Burt, W. J. Curry, C. F. Inglehearn; Null Mutation in the Chicken Mpdz/mupp1 Gene Causes Retinal Dysplasia and Degeneration: A New Candidate Gene for Human Retinitis Pigmentosa. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6352.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : To identify the gene defect that causes blindness in the sex-linked recessively-inherited retinal dysplasia and degeneration (rdd) chicken.

Methods: : Routine histology was performed on the birds. Previously uncharacterised microsatellite markers from chicken chromosome Z were genotyped on 77 progeny of a carrier male (rdd/+) and an affected female (rdd/W), and candidate genes were sequenced. The human orthologous gene was screened in a panel of archival DNAs from patients with retinitis pigmentosa using melting curve analysis and DNA sequencing.

Results: : The pathological defect in rdd birds became visible as undulations in the outer nuclear, the outer plexiform and the inner nuclear layers before E19 but after E12 in the bird’s life cycle. The rdd locus was refined to a ~3.0Mb region on chromosome Z. Sequence analysis of the MPDZ/mupp1 gene identified a C->T change that created a premature stop codon mutation (c.1372C->T, p.R458X), which segregated with the rdd phenotype as expected in a recessive manner. The screen to identify the human equivalent disease found 4 novel missense variants and 2 null mutations in the orthologous gene though their pathogenicity could not be confirmed.

Conclusions: : We have found that a null mutation in the chicken MPDZ/mupp1 gene causes the rdd phenotype and suggest that the corresponding human orthologue may be a candidate gene for human retinitis pigmentosa.

Keywords: genetics • retinal degenerations: hereditary • mutations 
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