Key Points
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Powerful statistical methods are available for the analysis of quantitative traits in experimental species. To a large extent, the development of these methods has been driven by the increased availability of molecular genetic markers and the generation of high-resolution genetic maps.
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Three broadly different types of statistical analysis can be used in the search for quantitative trait loci (QTL): single-marker tests, interval mapping and composite interval mapping. The advantage of composite interval mapping methods is that they accommodate multiple QTL.
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However, none of the existing methods can accommodate the full complexity of multifactorial traits that arise because of extensive gene-by-gene (epistatic) and gene-by-environment interactions. This is an area of active research and a recent computational approach provides a framework for the analysis of this problem, in which QTL number is estimated first, followed by QTL effect and locations.
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Another statistical issue that is the subject of debate concerns how to assess the statistical significance of any model of a complex trait. Computational simulation and non-parametric resampling are two methods that are being used.
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Despite the power of the statistical methods, and the wealth of genetic markers, there are few examples in which the genetic basis of a quantitative trait has been thoroughly dissected.
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One exciting view of the future is to consider functional genomics approaches. Transcriptional profiling in particular could provide a way to move rapidly towards a more comprehensive view of gene interactions and epistasis.
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Lessons learned from the statistical (QTL) analysis of complex phenotypes have the potential to be applied to an analysis of the variation of gene expression, and in this way a more complete understanding of functional networks of genes and their action might arise. This knowledge could benefit our current ability to understand the connection between phenotype and genotype.
Abstract
Simple statistical methods for the study of quantitative trait loci (QTL), such as analysis of variance, have given way to methods that involve several markers and high-resolution genetic maps. As a result, the mapping community has been provided with statistical and computational tools that have much greater power than ever before for studying and locating multiple and interacting QTL. Apart from their immediate practical applications, the lessons learnt from this evolution of QTL methodology might also be generally relevant to other types of functional genomics approach that are aimed at the dissection of complex phenotypes, such as microarray assessment of gene expression.
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Acknowledgements
This work is partially supported by the USDA-IFAFS. An extended thank you to the Teuscher group for allowing access and use of their data, and to the anonymous reviewers for many challenging opinions.
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An alphabetical list of genetic analysis software
Glossary
- COMPLEX TRAIT
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A trait determined by many genes, almost always interacting with environmental influences.
- QUANTITATIVE TRAIT LOCUS
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A genetic locus identified through the statistical analysis of complex traits (such as plant height or body weight). These traits are typically affected by more than one gene, and also by the environment.
- EPISTASIS
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In the broad sense used here, it refers to any genetic interaction in which the combined phenotypic effect of two or more loci exceeds the sum of effects at individual loci.
- RECOMBINANT INBRED LINES
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A population of fully homozygous individuals that is obtained by repeated selfing from an F1 hybrid, and that comprises ∼50% of each parental genome in different combinations.
- SEGREGATION DISTORTION
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The non-random segregation of alleles. Apparent segregation distortion can result from incorrect genotype classification.
- CLOSED FORM ESTIMATE
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An estimate of a population parameter that can be calculated directly from an equation to obtain an exact solution.
- SIGNIFICANCE LEVEL
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A probability for a test statistic that gives the maximum acceptable value of rejecting a 'true' null hypothesis.
- GENETIC INTERFERENCE
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The presence of a recombinational event in one region affects the occurrence of recombinational events in adjacent regions.
- GHOST QTL
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Quantitative trait locus (QTL) effects that occur as artefacts due to real QTL in surrounding intervals.
- GENETIC ALGORITHM
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Numerical optimization procedures based on evolutionary principles, such as mutation, deletion and selection.
- DENDROGRAM
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A branching 'tree' diagram that represents a hierarchy of categories on the basis of degree of similarity or number of shared characteristics, especially in biological taxonomy. The results of hierarchical clustering are presented as dendrograms, in which the distance along the tree from one element to the next represents their relative degree of similarity in terms of gene expression.
- NON-PARAMETRIC
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Statistical procedures that are not based on models, or assumptions pertaining to the distribution of the quantitative trait.
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Doerge, R. Mapping and analysis of quantitative trait loci in experimental populations. Nat Rev Genet 3, 43–52 (2002). https://doi.org/10.1038/nrg703
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DOI: https://doi.org/10.1038/nrg703
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