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PMID: 22345610 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A general Bayesian approach to analyzing diallel crosses of inbred strains.

Genetics ·Vol. 190 ·No. 2 ·2012-02-00 ·Pages 413-35

Lenarcic AB, Svenson KL, Churchill GA, Valdar W

Abstract

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.

MeSH Terms
Algorithms Alleles Animals Bayes Theorem Breeding Computer Simulation Crosses, Genetic Female Male Mice Mice, Inbred Strains/genetics Models, Genetic Phenotype
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Lenarcic Alan B
Department of Genetics and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599-7265, USA.
Svenson Karen L
Churchill Gary A
Valdar William
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Article Info
Journal
Genetics
Abbr.
Genetics
ISSN
1943-2631
Published
2012-02-00
Pages
413-35
Language
English
Region
United States
NLM ID
0374636
PMCID
PMC3276624
Subset
IM
Grants
NHGRI NIH HHS · P50 HG006582 · United States
NIMH NIH HHS · P50 MH006582 · United States
NIGMS NIH HHS · GM076468 · United States
NIMH NIH HHS · P50 MH090338 · United States
Medical Research Council · G0701612 · United Kingdom
NIGMS NIH HHS · P50 GM076468 · United States
NIGMS NIH HHS · R01 GM070683 · United States
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