Dissection of genetically complex traits with extremely large pools of yeast segregants

Most heritable traits, including many human diseases, are caused by multiple loci. Studies in both humans and model organisms, such as yeast, have failed to detect a large fraction of the loci that underlie such complex traits. A lack of statistical power to identify multiple loci with small effects...

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Bibliographic Details
Published in:Nature (London) 2010-04, Vol.464 (7291), p.1039-1042
Main Authors: Kruglyak, Leonid, Ehrenreich, Ian M, Torabi, Noorossadat, Jia, Yue, Kent, Jonathan, Martis, Stephen, Shapiro, Joshua A, Gresham, David, Caudy, Amy A
Format: Article
Language:English
Subjects:
4-Nitroquinoline-1-oxide - pharmacology
Biological and medical sciences
Chromosome Mapping - methods
Complexity
Crosses, Genetic
Diploidy
Dissection
DNA repair
Dominance (Genetics)
Drug resistance
Drug Resistance, Fungal - drug effects
Drug Resistance, Fungal - genetics
Fundamental and applied biological sciences. Psychology
Gene Frequency
Genes
Genes. Genome
Genetic research
Genetics
Genomics
Genotype
Haploidy
Human
Loci
Mathematical models
Methods
Mitochondria - metabolism
Molecular and cellular biology
Molecular genetics
Multifactorial Inheritance - genetics
Oligonucleotide Array Sequence Analysis
Organisms
Phenotype
Polymorphism, Single Nucleotide - genetics
Pools
Properties
Quantitative Trait Loci - genetics
Quinolones - pharmacology
Saccharomyces cerevisiae
Saccharomyces cerevisiae - cytology
Saccharomyces cerevisiae - drug effects
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - metabolism
Sample Size
Yeast
Yeast fungi
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Summary:Most heritable traits, including many human diseases, are caused by multiple loci. Studies in both humans and model organisms, such as yeast, have failed to detect a large fraction of the loci that underlie such complex traits. A lack of statistical power to identify multiple loci with small effects is undoubtedly one of the primary reasons for this problem. We have developed a method in yeast that allows the use of much larger sample sizes than previously possible and hence permits the detection of multiple loci with small effects. The method involves generating very large numbers of progeny from a cross between two Saccharomyces cerevisiae strains and then phenotyping and genotyping pools of these offspring. We applied the method to 17 chemical resistance traits and mitochondrial function, and identified loci for each of these phenotypes. We show that the level of genetic complexity underlying these quantitative traits is highly variable, with some traits influenced by one major locus and others by at least 20 loci. Our results provide an empirical demonstration of the genetic complexity of a number of traits and show that it is possible to identify many of the underlying factors using straightforward techniques. Our method should have broad applications in yeast and can be extended to other organisms.
ISSN:0028-0836
1476-4687
DOI:10.1038/nature08923