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    J. Riksen

    The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in... more
    The number and distribution of gene expression QTL (eQTL) represent the genetic architecture of many complex traits, including common human diseases. We previously reported that the heritable eQTL patterns are highly dynamic with age in an N2 × CB4856 recombinant inbred population of the nematode Caenorhabditis elegans. In particular, we showed that the number of eQTL decreased with age. Here, we investigated the reason for this decrease by combining gene expression profiles at three ages in the wild types N2 and CB4856 with the reported expression profiles of the RIL population. We determined heritability and transgression (when gene expression levels in the RILs are more extreme than the parents) and investigated their relation with eQTL changes with age. Transgressive segregation was widespread but depended on physiological age. The percentage of genes with an eQTL increased with a higher heritability in young worms. However, for old worms this percentage hardly increased. Using ...
    C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical... more
    C. elegans is extensively used to study the Wnt-pathway and most of the core-signalling components are known. Four β-catenins are important gene expression regulators in Wnt-signalling. One of these, bar-1, is part of the canonical Wnt-pathway. Together with Wnt effector pop-1, bar-1 forms a transcription activation complex which regulates the transcription of downstream genes. The effects of bar-1 loss-of-function mutations on many phenotypes have been studied well. However, the effects on global gene expression are unknown. Here we report the effects of a loss-of-function mutation bar-1(ga80). By analysing the transcriptome and developmental phenotyping we show that bar-1(ga80) impairs developmental timing. This developmental difference confounds the comparison of the gene expression profile between the mutant and the reference strain. When corrected for this difference it was possible to identify genes that were directly affected by the bar-1 mutation. We show that the Wnt-pathway itself is activated, as well as transcription factors elt-3, pqm-1, mdl-1 and pha-4 and their associated genes. The outcomes imply that this response compensates for the loss of functional bar-1. Altogether we show that bar-1 loss-of function leads to delayed development possibly caused by an induction of a stress response, reflected by daf-16 activated genes.
    Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the evolution of life histories. Knowledge of the molecular genetic basis of plasticity and GEI provides insight into the underlying mechanisms of... more
    Phenotypic plasticity and genotype-environment interactions (GEI) play an important role in the evolution of life histories. Knowledge of the molecular genetic basis of plasticity and GEI provides insight into the underlying mechanisms of life-history changes in different environments. We used a genomewide single-nucleotide polymorphism map in a recombinant N2 x CB4856 inbred panel of the nematode Caenorhabditis elegans to study the genetic control of phenotypic plasticity to temperature in four fitness-related traits, that is, age at maturity, fertility, egg size and growth rate. We mapped quantitative trait loci (QTL) for the respective traits at 12 and 24 degrees C, as well as their plasticities. We found genetic variation and GEI for age at maturity, fertility, egg size and growth rate. GEI in fertility and egg size was attributed to changes in rank order of reaction norms. In case of age at maturity and growth rate, GEI was caused mainly by differences in the among-line variance. In total, 11 QTLs were detected, five QTL at 12 degrees C and six QTL at 24 degrees C, which were associated with life-history traits. Five QTL associated with age at maturity, fertility and growth rate showed QTL x environment interaction. These colocalized with plasticity QTL for the respective traits suggesting allelic sensitivity to temperature. Further fine mapping, complementation analyses and gene silencing are planned to identify candidate genes underlying phenotypic plasticity for age at maturity, fertility and growth.