title: Mutation in the guanine nucleotide-binding protein beta-3 causes retinal degeneration and embryonic mortality in chickens.
abstract: OBJECTIVE
  To identify the gene defect that causes blindness and the predisposition to embryonic death in the retinopathy globe enlarged (rge) chicken.
  
  
  METHODS
  Linkage analysis, with previously uncharacterized microsatellite markers from chicken chromosome 1, was performed on 138 progeny of an rge/+ and an rge/rge cross, and candidate genes were sequenced.
  
  
  RESULTS
  The rge locus was refined and the gene for guanine nucleotide-binding protein beta-3 (GNB3), which encodes a cone transducin beta subunit, was found to have a 3-bp deletion (D153del) that segregated with the rge phenotype. This mutation deleted a highly conserved aspartic acid residue in the third of seven WD domains in GNB3. In silico modeling suggested that this mutation destabilized the protein. Furthermore, a 70% reduction was found in immunoreactivity to anti-GNB3 in the rge-affected retina.
  
  
  CONCLUSIONS
  These findings implicate the beta-subunit of cone transducin as the defective protein underlying the rge phenotype. Furthermore, GNB3 is ubiquitously expressed, and the c.825C-->T GNB3 splicing variant (MIM 139130) has been associated with hypertension, obesity, diabetes, low birth weight, coronary heart disease, and stroke in the human population. It therefore seems likely that the defect underlying these human diseases also causes reduced embryonic viability in the rge chicken, making it a powerful model for studying the pathology involved in these associations.
authors.affiliation: Molecular Vision Group, School of Contemporary Sciences, University of Abertay, Dundee DD1 1HG, United Kingdom.
authors.forename: Hemanth
authors.initials: H
authors.lastname: Tummala
authors.forename: Manir
authors.initials: M
authors.lastname: Ali
authors.forename: Paul
authors.initials: P
authors.lastname: Getty
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hocking
authors.forename: David W
authors.initials: DW
authors.lastname: Burt
authors.forename: Chris F
authors.initials: CF
authors.lastname: Inglehearn
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Lester
mesh_terms: D000818:Animals; D001766:Blindness / Q000235:genetics; D002642:Chick Embryo; D002645:Chickens / Q000235:genetics*; D047108:Embryonic Development; D005123:Eye / Q000473:pathology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D005838:Genotype; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics*; D006984:Hypertrophy; D015151:Immunoblotting; D018895:Microsatellite Repeats; D009154:Mutation; D011201:Poultry Diseases / Q000401:mortality*; D012333:RNA, Messenger / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics* / Q000401:mortality*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015293:Transducin / Q000235:genetics
chemical_list: C454420:G-protein beta3 subunit; D012333:RNA, Messenger; D020962:Heterotrimeric GTP-Binding Proteins; D015293:Transducin