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Functional mapping — how to map and study the genetic architecture of dynamic complex traits

Abstract

The development of any organism is a complex dynamic process that is controlled by a network of genes as well as by environmental factors. Traditional mapping approaches for analysing phenotypic data measured at a single time point are too simple to reveal the genetic control of developmental processes. A general statistical mapping framework, called functional mapping, has been proposed to characterize, in a single step, the quantitative trait loci (QTLs) or nucleotides (QTNs) that underlie a complex dynamic trait. Functional mapping estimates mathematical parameters that describe the developmental mechanisms of trait formation and expression for each QTL or QTN. The approach provides a useful quantitative and testable framework for assessing the interplay between gene actions or interactions and developmental changes.

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Figure 1: Four representative patterns for the genetic control of growth trajectories by a dynamic QTL.
Figure 2: Pleiotropic QTL effects on vegetative growth and reproductive behaviour.

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Acknowledgements

The authors thank the three anonymous referees for their constructive comments that have improved the presentation of this manuscript. This work was supported by an Outstanding Young Investigator Award of the National Natural Science Foundation of China, a University of Florida Research Opportunity Fund, a University of South Florida Biodefense grant and the National Institutes of Health.

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Glossary

Allometry

The change in proportion of various parts of an organism as a consequence of growth.

Allometric scaling law

Metabolic rates or other biological variables that scale as multiples of one-quarter of body mass.

Biexponential equation

An equation that describes two subsequent processes in which the responses change exponentially with a variable in each process.

Dynamic biological thermal function

A function that describes the change of growth rate or other variables of an organism with different temperatures.

Exercise stress test

A general screening tool to test the effect of exercise on the heart.

Finite mixture model

A type of density model that comprises several component functions, usually Gaussian functions, which are combined to provide a multimodal density.

Fourier series equation

An expansion of a periodic function in terms of an infinite sum of sines and cosines.

Linkage disequilibrium

The non-random co-segregation of alleles at different loci in a population.

Log-likelihood ratio

A test statistic that is expressed as the log ratio of the maximum value of the likelihood function under the constraint of the null hypothesis to the maximum value without that constraint.

Logistic equation

Also called an S-shaped curve. It models a process of growth in which the initial stage of growth is approximately exponential. As competition arises, the growth slows, and at maturity, growth stops.

Model selection

A process in which the best model is selected from many competing models that fit the data.

Polynomial

Functions that have the form f(x) = anxn + a−1xn−1 + ... + a1x + a0, where n is a non-negative integer.

Shrinkage estimation

An estimating procedure by which all candidate variables are taken into account in the model, but their estimated effects are forced to shrink towards zero.

Wavelet transform approach

An approach that compresses high-order dimensional data to a low-order representation without losing the original information.

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Wu, R., Lin, M. Functional mapping — how to map and study the genetic architecture of dynamic complex traits. Nat Rev Genet 7, 229–237 (2006). https://doi.org/10.1038/nrg1804

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