Publication Date:
2010-04-16
Description:
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.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862354/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2862354/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ehrenreich, Ian M -- Torabi, Noorossadat -- Jia, Yue -- Kent, Jonathan -- Martis, Stephen -- Shapiro, Joshua A -- Gresham, David -- Caudy, Amy A -- Kruglyak, Leonid -- F32 HG005176/HG/NHGRI NIH HHS/ -- F32 HG005176-01/HG/NHGRI NIH HHS/ -- F32 HG51762/HG/NHGRI NIH HHS/ -- P50 GM071508/GM/NIGMS NIH HHS/ -- P50 GM071508-01/GM/NIGMS NIH HHS/ -- R37 MH059520/MH/NIMH NIH HHS/ -- R37 MH059520-13/MH/NIMH NIH HHS/ -- R37 MH59520/MH/NIMH NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2010 Apr 15;464(7291):1039-42. doi: 10.1038/nature08923.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey 08540, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20393561" target="_blank"〉PubMed〈/a〉
Keywords:
4-Nitroquinoline-1-oxide/pharmacology
;
Chromosome Mapping/*methods
;
Crosses, Genetic
;
Diploidy
;
Drug Resistance, Fungal/drug effects/genetics
;
Gene Frequency
;
Genotype
;
Haploidy
;
Mitochondria/metabolism
;
Multifactorial Inheritance/*genetics
;
Oligonucleotide Array Sequence Analysis
;
Phenotype
;
Polymorphism, Single Nucleotide/genetics
;
Quantitative Trait Loci/*genetics
;
Quinolones/pharmacology
;
Saccharomyces cerevisiae/cytology/drug effects/*genetics/metabolism
;
Sample Size
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
