Allelic penetrance approach as a tool to model twolocus - Sepúlveda, N; Paulino, C.D; Carneiro, J; Penha-Gonçalves, C
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
The multigenic structure of the MHC locus contributes to positive selection efficiency: A role for MHC class II gene-genespecific - Caetano Monteiro, M.; Couceiro, S.; Penha-Gonçalves, C.
The study of T cell positive selection in the thymus has long been focused on the
specificity of the MHC-TCR interactions, making use of genetically manipulated mice
that display TCR specificities or selecting peptides of limited diversity. However, little is
known on the role of the MHC molecules irrespective of the peptide specificity and the
implications of MHC multigenic structure in thymic positive selection have not been
addressed. Here, we investigated the effect of MHC class II genetic configuration on the
positive selection efficiency of naturally generated pre-selection repertoires in the
mouse thymus. Analysis of positively selected thymocyte populations in MHC-congenic
and -transgenic mice revealed that expression of...
Mapping of quantitative trait loci using the skew-normal distribution - Fernandes, Elisabete; Pacheco, António; Penha-Gonçalves, Carlos
In standard interval mapping (IM) of quantitative trait loci (QTL), the QTL effect is described by a normal mixture
model. When this assumption of normality is violated, the most commonly adopted strategy is to use the previous model after data
transformation. However, an appropriate transformation may not exist or may be difficult to find. Also this approach can raise
interpretation issues. An interesting alternative is to consider a skew-normal mixture model in standard IM, and the resulting
method is here denoted as skew-normal IM. This flexible model that includes the usual symmetric normal distribution as a special
case is important, allowing continuous variation from normality...
Irf4 is a positional and functional candidate gene for the control of serum IgM levels in the mouse - Côrte-Real, J; Rodo, J; Almeida, P; Coutinho, A; Demengeot, J; Penha-Gonçalves, C
Natural IgM are involved in numerous immunological functions but the genetic factors that control the homeostasis of its
secretion and upholding remain unknown. Prompted by the finding that C57BL/6 mice had significantly lower serum levels of
IgM when compared with BALB/c mice, we performed a genome-wide screen and found that the level of serum IgM was
controlled by a QTL on chromosome 13 reaching the highest level of association at marker D13Mit266 (LOD score¼3.54).
This locus was named IgMSC1 and covered a region encompassing the interferon-regulatory factor 4 gene (Irf4). The number
of splenic mature B cells in C57BL/6 did not differ from BALB/c mice...
Bayesian analysis of allelic penetrance models for complex binary traits - Sepúlveda, N; Paulino, C.D.; Penha-Gonçalves, C.
Complex 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...
Modelos de interacção genética de dois genes em fenótipos - Sepúlveda, N; Paulino, C.D.; Penha-Gonçalves, C.
Em trabalhos anteriores foram propostos diversos modelos estatísticos para a penetrância de forma a inferir a interacção de dois genes dial´elicos na construção de
fenótipos binários complexos: modelos de acção independente, modelos de inibição e
modelos de número mínimo de alelos. Estes modelos baseiam-se numa decomposição
da penetrância através da abordagem por penetrâncias alélicas, que permitiu a inclusão dos conceitos mendelianos de dominância e recessividade alélica na sua modelação. Pretende-se aqui dar a conhecer os avanços mais recentes na parte da modelação
da interacção genética, apresentando uma nova decomposição da penetrância e uma
nova formulação matemática da dominância e da recessividade. Aplicam-se ainda ferramentas bayesianas...