• Blangero, John (PI)

    Project: Research project

    Project Details


    Thyroid hormones are critically important in many metabolic and
    physiological processes. However, there is very little information on
    how normal variation in thyroid hormone phenotypes is genetically
    mediated. The overall objective of this proposal is to detect genetic
    effects on normal thyroid hormone variation in an animal model, the
    baboon, by statistical genetic analysis of pedigree data. Complex
    segregation analysis will be used to determine the effects of major
    genes, polygenic factors, and a known polymorphic candidate locus on
    several quantitative dimensions of thyroid hormone variation including
    thyroid hormone secretion, thyroid hormone metabolism, thyroid hormone
    transport, and thyroid hormone action. Specifically, serum concentrations of thyroglobulin, total thyroxine,
    free thyroxine, total triiodothyronine, free triiodothyronine, reverse
    triiodothyronine, thyroxine-binding globulin, sex hormone binding
    globulin, and osteocalcin will be measured in 600 pedigreed baboons.
    Each animal's genotype at a polymorphic candidate locus, thyroxine-
    binding globulin (TBG), will be assessed. Using quantitative genetic
    methods, the heritabilities of each trait and the genetic correlations
    between traits will be estimated. Complex segregation analysis will be
    used to detect major genes influencing these thyroid hormone phenotypes
    and to examine the joint effects of major genes, polygenes, and the TBG
    polymorphism. Extensions of segregation analysis will be used to detect
    differential expression of genotypes as a function of covariates such as
    sex and age. Current statistical genetic techniques will be extended to allow for
    multiple quantitative phenotypes and new multivariate statistical
    genetic methods will be developed. These methods will provide increased
    power to detect subtle effects of major loci on quantitative traits.
    These multivariate segregation analysis methods will be used to detect
    pleiotropic effects of major genes influencing different aspects of
    thyroid hormone variation and to examine interactions between loci. The proposed project will increase our knowledge about the genetic
    determinants of thyroid hormone variation, provide information on the
    extent of genetic covariation among related thyroid hormone phenotypes,
    help establish the baboon as a model for endocrine genetics, and provide
    new tools for multivariate genetic analysis.
    Effective start/end date9/30/929/29/97


    • National Institutes of Health: $143,581.00
    • National Institutes of Health: $114,253.00


    • Medicine(all)


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