Allelic transcripts dosage effect in morphologically normal ovarian cells from heterozygous carriers of a BRCA1/2 French Canadian founder mutation.

We hypothesized that the transcriptome of primary cultures of morphologically normal ovarian surface epithelial cells could be altered by the presence of a heterozygous BRCA1 or BRCA2 mutation. We aimed to discover early events associated with ovarian carcinogenesis, which could represent putative targets for preventive strategies of this silent killer tumor. We identified the first molecular signature associated with French Canadian BRCA1 or BRCA2 founder mutations in morphologically normal ovarian epithelial cells. We discovered that wild-type and mutated BRCA2 allelic transcripts were expressed not only in morphologically normal but also in tumor cells from BRCA2-8765delAG carriers. Further analysis of morphologically normal ovarian and tumor cells from BRCA1-4446C>T carriers lead to the same observation. Our data support the idea that one single hit in BRCA1 or BRCA2 is sufficient to alter the transcriptome of phenotypically normal ovarian epithelial cells. The highest level of BRCA2-mutated allele transcript expression was measured in cells originating from the most aggressive ovarian tumor. The penetrance of the mutation and the aggressiveness of the related tumor could depend on a dosage effect of the mutated allele transcript.

Natural variation in the molecular stress network correlates with a behavioural syndrome.

In several species, individuals from the same population behave differently from each other. A functional link between variation in personality traits and the stress response has been suggested by studies in artificial selection lines in fish, birds and mammals. The aim of this study was to test whether the expression of genes involved in the stress response co-varies with personality traits in a natural population. Four personality traits, excreted cortisol level and brain expression of six candidate genes (CRF, CRF-R2, POMC1, GR1, GR2, MR) were measured in non-stressed wild-caught threespine sticklebacks (Gasterosteus aculeatus). We found correlations between variation in personality traits and variation in the expression of genes involved in the stress response. Aggressiveness was negatively correlated with cortisol levels. Boldness and aggressiveness formed a behavioural syndrome and were both positively correlated with brain expression of glucocorticoid receptors (GR1 and GR2). Boldness and exploration were positively correlated with expression of POMC1 but not with each other. Our results are compatible with a model that suggests that the aggressiveness-boldness behavioural syndrome could be the consequence of a physiological pleiotropic effect of glucocorticoid receptors, which are involved in the stress response and behaviour variation.