Browsing by Author "Paulino, Carlos Daniel"
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- Allelic penetrance approach as a tool to model twolocusPublication . Sepúlveda, Nuno; Paulino, Carlos Daniel; Carneiro, Jorge; Penha-Gonçalves, CarlosMany 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.
- Bayesian analysis of allelic penetrance models for complex binary traitsPublication . Sepúlveda, Nuno; Paulino, Carlos Daniel; Penha-Gonçalves, CarlosComplex binary traits result from an intricate network of genetic and environmental factors. To aid their genetic dissection, several generalized linear models have been described to detect interaction between genes. However, it is recognized that these models have limited genetic interpretation. To overcome this problem, the allelic penetrance approach was proposed to model the action of a dominant or a recessive allele at a single locus, and to describe two-locus independent, inhibition, and cumulative actions. Classically, a recessive inheritance requires the expression of both recessive alleles in homozygotes to obtain the phenotype (type I recessiveness). In previous work, recessiveness was defined alternatively as a situation where a recessive allele is able to express the phenotype when the dominant allele is not active (type II recessiveness). Both definitions of recessiveness are then discussed under the allelic penetrance models. Bayesian methods are applied to analyze two data sets: one regarding the effect of the haplotype [HLA-B8, SC01, DR3] on the inheritance of IgD and IgG4 immunoglobulin deficiencies in humans, and other related to two-locus action in the control of Listeria infection susceptibility in mice.