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Allelic penetrance approach as a tool to model twolocus
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Advisor(s)
Abstract(s)
Many binary phenotypes do not follow a classical Mendelian
inheritance pattern. Interaction between genetic and environmental
factors is thought to contribute to the incomplete
penetrance phenomena often observed in these complex
binary traits. Several two-locus models for penetrance have
been proposed to aid the genetic dissection of binary traits.
Such models assume linear genetic effects of both loci in
different mathematical scales of penetrance, resembling the
analytical framework of quantitative traits. However, changes
in phenotypic scale are difficult to envisage in binary traits
and limited genetic interpretation is extractable from current
modeling of penetrance. To overcome this limitation, we
derived an allelic penetrance approach that partitioned
incomplete penetrance into the alleles controlling the
phenotype and into the genetic background and environmental
factors. We applied this approach to formulate
dominance and recessiveness in a single biallelic locus and
to model different genetic mechanisms for the joint action of
two biallelic loci. We fit the models to data on the
susceptibility of mice following infections with Listeria
monocytogenes and Plasmodium berghei. These models
gain in genetic interpretation, because they specify the
alleles that are responsible for the genetic (inter)action and
their genetic nature (dominant or recessive), and predict
genotypic combinations determining the phenotype. Further,
we show via computer simulations that the proposed models
produce penetrance patterns not captured by traditional twolocus
models. This approach provides a new analysis
framework for dissecting mechanisms of interlocus joint
action in binary traits using genetic crosses.
Description
Keywords
Reduced penetrance Allelic penetrance External penetrance Epistasis
Citation
Sepulveda, N., Paulino, C.D., Carneiro, J., Penha Gonçalves, C. (2007). Allelic penetrance approach as a tool to model two-locus interaction in complex binary traits. Heredity 99(2) :1-13