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

Amanda Vinson, Kamm Prongay, Betsy Ferguson

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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

Keywords

  • Complex disease
  • Pedigree
  • Quantitative trait
  • Rhesus macaque

ASJC Scopus subject areas

  • Animal Science and Zoology
  • General Biochemistry, Genetics and Molecular Biology

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