Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity

Douglas H. Lester, C F Inglehearn, R Bashir, H Ackford, L Esakowitz, M Jay, A C Bird, A F Wright, S S Papiha, S S Bhattacharya

    Research output: Contribution to journalArticle

    13 Citations (Scopus)

    Abstract

    Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome.

    Original languageEnglish
    Pages (from-to)536-541
    Number of pages6
    JournalAmerican Journal of Human Genetics
    Volume47
    Issue number3
    Publication statusPublished - Sep 1990

    Fingerprint

    Retinitis Pigmentosa
    Genetic Heterogeneity
    Rhodopsin
    Penetrance
    Lod Score
    Mutation
    Codon
    Pedigree
    Point Mutation
    Oligonucleotides
    Genetic Recombination
    Genes
    Sequence Analysis
    Genome

    Cite this

    Lester, D. H., Inglehearn, C. F., Bashir, R., Ackford, H., Esakowitz, L., Jay, M., ... Bhattacharya, S. S. (1990). Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity. American Journal of Human Genetics, 47(3), 536-541.
    Lester, Douglas H. ; Inglehearn, C F ; Bashir, R ; Ackford, H ; Esakowitz, L ; Jay, M ; Bird, A C ; Wright, A F ; Papiha, S S ; Bhattacharya, S S. / Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another : confirmation of genetic heterogeneity. In: American Journal of Human Genetics. 1990 ; Vol. 47, No. 3. pp. 536-541.
    @article{cfe70865fdfd4d6aaa5fc0449c027fd9,
    title = "Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity",
    abstract = "Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome.",
    author = "Lester, {Douglas H.} and Inglehearn, {C F} and R Bashir and H Ackford and L Esakowitz and M Jay and Bird, {A C} and Wright, {A F} and Papiha, {S S} and Bhattacharya, {S S}",
    year = "1990",
    month = "9",
    language = "English",
    volume = "47",
    pages = "536--541",
    journal = "American Journal of Human Genetics",
    issn = "0002-9297",
    publisher = "Cell Press",
    number = "3",

    }

    Lester, DH, Inglehearn, CF, Bashir, R, Ackford, H, Esakowitz, L, Jay, M, Bird, AC, Wright, AF, Papiha, SS & Bhattacharya, SS 1990, 'Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another: confirmation of genetic heterogeneity', American Journal of Human Genetics, vol. 47, no. 3, pp. 536-541.

    Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another : confirmation of genetic heterogeneity. / Lester, Douglas H.; Inglehearn, C F; Bashir, R; Ackford, H; Esakowitz, L; Jay, M; Bird, A C; Wright, A F; Papiha, S S; Bhattacharya, S S.

    In: American Journal of Human Genetics, Vol. 47, No. 3, 09.1990, p. 536-541.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Linkage to D3S47 (C17) in one large autosomal dominant retinitis pigmentosa family and exclusion in another

    T2 - confirmation of genetic heterogeneity

    AU - Lester, Douglas H.

    AU - Inglehearn, C F

    AU - Bashir, R

    AU - Ackford, H

    AU - Esakowitz, L

    AU - Jay, M

    AU - Bird, A C

    AU - Wright, A F

    AU - Papiha, S S

    AU - Bhattacharya, S S

    PY - 1990/9

    Y1 - 1990/9

    N2 - Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome.

    AB - Recently Dryja and his co-workers observed a mutation in the 23d codon of the rhodopsin gene in a proportion of autosomal dominant retinitis pigmentosa (ADRP) patients. Linkage analysis with a rhodopsin-linked probe C17 (D3S47) was carried out in two large British ADRP families, one with diffuse-type (D-type) RP and the other with regional-type (R-type) RP. Significantly positive lod scores (lod score maximum [Zmax] = +5.58 at recombination fraction [theta] = .0) were obtained between C17 and our D-type ADRP family showing complete penetrance. Sequence and oligonucleotide analysis has, however, shown that no point mutation at the 23d codon exists in affected individuals in our complete-penetrance pedigree, indicating that another rhodopsin mutation is probably responsible for ADRP in this family. Significantly negative lod scores (Z less than -2 at theta = .045) were, however, obtained between C17 and our R-type family which showed incomplete penetrance. Previous results presented by this laboratory also showed no linkage between C17 and another large British R-type ADRP family with incomplete penetrance. This confirms genetic heterogeneity. Some types of ADRP are being caused by different mutations in the rhodopsin locus (3q21-24) or another tightly linked gene in this region, while other types of ADRP are the result of mutations elsewhere in the genome.

    M3 - Article

    C2 - 2393026

    VL - 47

    SP - 536

    EP - 541

    JO - American Journal of Human Genetics

    JF - American Journal of Human Genetics

    SN - 0002-9297

    IS - 3

    ER -