The value of extended pedigrees for next-generation analysis of complex disease in the rhesus macaque

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    7 Citations (Scopus)

    Abstract

    Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease.

    Original languageEnglish (US)
    Article numberilt041
    Pages (from-to)91-105
    Number of pages15
    JournalILAR Journal
    Volume54
    Issue number2
    DOIs
    StatePublished - Nov 2013

    Fingerprint

    Pedigree
    Macaca mulatta
    pedigree
    human diseases
    Genetic Linkage
    quantitative traits
    cohort studies
    noninsulin-dependent diabetes mellitus
    cardiovascular diseases
    linkage (genetics)
    genetic techniques and protocols
    human health
    heritability
    Type 2 Diabetes Mellitus
    Medical problems
    risk factors
    Cohort Studies
    Cardiovascular Diseases
    Genome
    environmental factors

    Keywords

    • Complex disease
    • Pedigree
    • Quantitative trait
    • Rhesus macaque

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)
    • Animal Science and Zoology

    Cite this

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    abstract = "Complex diseases (e.g., cardiovascular disease and type 2 diabetes, among many others) pose the biggest threat to human health worldwide and are among the most challenging to investigate. Susceptibility to complex disease may be caused by multiple genetic variants (GVs) and their interaction, by environmental factors, and by interaction between GVs and environment, and large study cohorts with substantial analytical power are typically required to elucidate these individual contributions. Here, we discuss the advantages of both power and feasibility afforded by the use of extended pedigrees of rhesus macaques (Macaca mulatta) for genetic studies of complex human disease based on next-generation sequence data. We present these advantages in the context of previous research conducted in rhesus macaques for several representative complex diseases. We also describe a single, multigeneration pedigree of Indian-origin rhesus macaques and a sample biobank we have developed for genetic analysis of complex disease, including power of this pedigree to detect causal GVs using either genetic linkage or association methods in a variance decomposition approach. Finally, we summarize findings of significant heritability for a number of quantitative traits that demonstrate that genetic contributions to risk factors for complex disease can be detected and measured in this pedigree. We conclude that the development and application of an extended pedigree to analysis of complex disease traits in the rhesus macaque have shown promising early success and that genome-wide genetic and higher order -omics studies in this pedigree are likely to yield useful insights into the architecture of complex human disease.",
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