4.4 Article

A General Bayesian Approach to Analyzing Diallel Crosses of Inbred Strains

期刊

GENETICS
卷 190, 期 2, 页码 413-U221

出版社

GENETICS SOCIETY AMERICA
DOI: 10.1534/genetics.111.132563

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资金

  1. National Institutes of Health (NIH) Center of Excellence in Genome Sciences [P50 MH090338, P50 MH006582]
  2. NIH [GM076468]
  3. Jackson Laboratory
  4. University of North Carolina Lineberger Comprehensive Cancer Center
  5. MRC [G0701612] Funding Source: UKRI
  6. Medical Research Council [G0701612] Funding Source: researchfish

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The classic diallel takes a set of parents and produces offspring from all possible mating pairs. Phenotype values among the offspring can then be related back to their respective parentage. When the parents are diploid, sexed, and inbred, the diallel can characterize aggregate effects of genetic background on a phenotype, revealing effects of strain dosage, heterosis, parent of origin, epistasis, and sex-specific versions thereof. However, its analysis is traditionally intricate, unforgiving of unplanned missing information, and highly sensitive to imbalance, making the diallel unapproachable to many geneticists. Nonetheless, imbalanced and incomplete diallels arise frequently, albeit unintentionally, as by-products of larger-scale experiments that collect F-1 data, for example, pilot studies or multiparent breeding efforts such as the Collaborative Cross or the Arabidopsis MAGIC lines. We present a general Bayesian model for analyzing diallel data on dioecious diploid inbred strains that cleanly decomposes the observed patterns of variation into biologically intuitive components, simultaneously models and accommodates outliers, and provides shrinkage estimates of effects that automatically incorporate uncertainty due to imbalance, missing data, and small sample size. We further present a model selection procedure for weighing evidence for or against the inclusion of those components in a predictive model. We evaluate our method through simulation and apply it to incomplete diallel data on the founders and F-1's of the Collaborative Cross, robustly characterizing the genetic architecture of 48 phenotypes.

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