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Proc Natl Acad Sci U S A DOI:10.1073/pnas.1407126111

Interactions between chromosomal and nonchromosomal elements reveal missing heritability.

Publication TypeJournal Article
Year of Publication2014
AuthorsEdwards, MD, Symbor-Nagrabska, A, Dollard, L, Gifford, DK, Fink, GR
JournalProc Natl Acad Sci U S A
Date Published2014 May 27
KeywordsAnalysis of Variance, Chromosomes, Computational Biology, Extrachromosomal Inheritance, Gene Frequency, Genetic Therapy, Humans, Mitochondrial Diseases, Models, Genetic, Phenotype, Polymorphism, Single Nucleotide, Yeasts

The measurement of any nonchromosomal genetic contribution to the heritability of a trait is often confounded by the inability to control both the chromosomal and nonchromosomal information in a population. We have designed a unique system in yeast where we can control both sources of information so that the phenotype of a single chromosomal polymorphism can be measured in the presence of different cytoplasmic elements. With this system, we have shown that both the source of the mitochondrial genome and the presence or absence of a dsRNA virus influence the phenotype of chromosomal variants that affect the growth of yeast. Moreover, by considering this nonchromosomal information that is passed from parent to offspring and by allowing chromosomal and nonchromosomal information to exhibit nonadditive interactions, we are able to account for much of the heritability of growth traits. Taken together, our results highlight the importance of including all sources of heritable information in genetic studies and suggest a possible avenue of attack for finding additional missing heritability.


Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID24825890
PubMed Central IDPMC4040555
Grant ListR01 GM035010 / GM / NIGMS NIH HHS / United States
GM035010 / GM / NIGMS NIH HHS / United States