Analysing the genome of small family structures

Initially, the DAMONA database was designed to identify de novo mutations. If a de novo mutation takes place within cells in the germline - the cells which are susceptible to forming the gametes (ovules or sperm cells) - of a given individual (father or mother) they will not be detectable in them but will be transmitted to the descendant conceived by the mutated gamete, who will then transmit it to half of their own descendants. During his doctoral studies, Chad Harland aimed to identify the classic de novo mutations for the entire DAMONA database. Classic mutations are those which involve the modification of one or a few nucleoties within a given sequence. Of the 750 individuals listed in the DAMONA database, there were 115 small family structures consisting of a ‘father-mother’ couple, one of their descendants and four or five individuals descended from this descendant. Charlier and her colleagues used this range of data to find ‘new retrotransposition’ type de novo mutations within these family structures. ‘We wanted to see the mobilisation of de novo elements similar to those found in the APOB gene within the germline’, she explains. ‘We were able to highlight five such de novo mutations among the 115 family structures available to us’. These mutations were therefore produced within a sperm cell or ovocyte of a father or a mother. Of these five mutations, four came from a male germline and one from a female germline. ‘This clearly shows that the this type of event can be triggered both in males and in females’  indicates Carole Charlier. ‘But we also realised, unexpectedly, that of the four de novo mutations which appeared in the males, three of them were produced in the germine of the same bull. Even more surprisingly, two of these three mutations had been transmitted by the very same sperm cell’ reveals the researcher. These significant results suggest that, at a specific point in time, an endogenous retroviral element was mobilised in the germline of this bull. The next stage for Carole Charlier’s team will be to find out whether there is, for this bull in particular (or others presenting the same type of events) an alteration of the genome defence mechanisms which are supposed to suppress the mobilisation of transposable elements.

In the context of another European project, the sequencing of the transcriptome of Holstein cattle is also underway. Carole Charlier and her colleagues already have the intention of using this new range of data to try to establish a correlation between the presence of transposable elements from one location on the genome of these animals and the level of gene transcription in or near to which the elements are inserted. ‘Some elements that we have found in the genome of Holstein or Belgian Blue cattle will very probably have a significant impact, given the significant genes in which they are inserted’, she says. At the very least, that the farmers’ call for a CDH detection test will have a domino effect on the Carole Charlier’s research and that of her team, which shows no signs of slowing down!