Mutation in the guanine nucleotide-binding protein β-3 causes retinal degeneration and embryonic mortality in chickens

Hemanth Tummala, Manir Ali, Paul Getty, Paul M Hocking, David W Burt, Chris F Inglehearn, Douglas H Lester

    Research output: Contribution to journalArticle

    Abstract

    Ppurpose. 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 β-3 (GNB3), which encodes a cone transducin β 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 β-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.

    Original languageEnglish
    Pages (from-to)4714-4718
    Number of pages5
    JournalInvestigative Ophthalmology & Visual Science
    Volume47
    Issue number11
    DOIs
    Publication statusPublished - Nov 2006

    Fingerprint

    Retinal Degeneration
    Guanine Nucleotides
    Guanine
    Chickens
    Carrier Proteins
    Mutation
    Mortality
    Transducin
    Proteins
    Protein Splicing
    Genes
    Phenotype
    Chromosomes, Human, Pair 1
    Low Birth Weight Infant
    Blindness
    Aspartic Acid
    Computer Simulation
    Microsatellite Repeats
    Coronary Disease
    Retina

    Cite this

    Tummala, Hemanth ; Ali, Manir ; Getty, Paul ; Hocking, Paul M ; Burt, David W ; Inglehearn, Chris F ; Lester, Douglas H. / Mutation in the guanine nucleotide-binding protein β-3 causes retinal degeneration and embryonic mortality in chickens. In: Investigative Ophthalmology & Visual Science. 2006 ; Vol. 47, No. 11. pp. 4714-4718.
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    abstract = "Ppurpose. 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 β-3 (GNB3), which encodes a cone transducin β 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 β-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.",
    author = "Hemanth Tummala and Manir Ali and Paul Getty and Hocking, {Paul M} and Burt, {David W} and Inglehearn, {Chris F} and Lester, {Douglas H}",
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    Mutation in the guanine nucleotide-binding protein β-3 causes retinal degeneration and embryonic mortality in chickens. / Tummala, Hemanth; Ali, Manir; Getty, Paul; Hocking, Paul M; Burt, David W; Inglehearn, Chris F; Lester, Douglas H.

    In: Investigative Ophthalmology & Visual Science, Vol. 47, No. 11, 11.2006, p. 4714-4718.

    Research output: Contribution to journalArticle

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    T1 - Mutation in the guanine nucleotide-binding protein β-3 causes retinal degeneration and embryonic mortality in chickens

    AU - Tummala, Hemanth

    AU - Ali, Manir

    AU - Getty, Paul

    AU - Hocking, Paul M

    AU - Burt, David W

    AU - Inglehearn, Chris F

    AU - Lester, Douglas H

    PY - 2006/11

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    N2 - Ppurpose. 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 β-3 (GNB3), which encodes a cone transducin β 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 β-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.

    AB - Ppurpose. 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 β-3 (GNB3), which encodes a cone transducin β 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 β-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.

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