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