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doi:10.1534/genetics.104.034447
A more recent version of this article appeared on December 1, 2004.
Regular Research Papers |
A Mechanistic Model for Genetic Machinery of Ontogenetic Growth
Rongling Wu 1*, Zuoheng Wang 1, Wei Zhao 1 and James Cheverud 2
1 University of Florida
2 Washington University
* To whom correspondence should be addressed. E-mail: rwu{at}stat.ufl.edu.
Submitted on August 5, 2004
Revised on September 2, 2004
Accepted on 3 September 2004
Two different genetic mechanisms can be proposed to explain variation in growth trajectories. The allelic sensitivity hypothesis states that growth trajectory is controlled by the time-dependent expression of alleles at the deterministic quantitative trait loci (dQTL) formed during embryogenesis. The gene regulation hypothesis states that the differentiation in growth process is due to the opportunistic quantitative trait loci (oQTL) through their mediation with new developmental signals. These two hypotheses of genetic control have been eluicidated in the literature. Here, we propose a new statistical model for discerning these two mechanisms in the context of growth trajectories by integrating growth laws within a QTL mapping framework. This model is developed within the maximum likelihood context, implemented with a grid approach for estimating the genomic positions of the deterministic and opportunistic QTL and the simplex algorithm for estimating the growth curve parameters of the genotypes at these QTL and the parameters modelling the residual (co)variance matrix. Our model allows for extensive hypothesis tests for the genetic control of growth processes and developmental events by these two types of QTL. The application of this new model to an F2 progeny in mice leads to the detection of deterministic and opportunistic QTL on chromosome 1 for mouse body mass growth. The estimates of QTL positions and effects from our model are broadly in agreement with those by traditional interval mapping approaches. The implications of this model for biological and biomedical research are discussed.
Key Words: Allelic sensitivity, Deterministic QTL, Gene regulatory control, Growth trajectory, Opportunistic QTL
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