An inconclusive first round

To find the gene containing the mutation responsible for the said phenotype, the researchers from the Unit of Animal Genomics, led by Michel Georges, went in search of a piece of  ancestral chromosome – a segment of chromosome where the mutation originally occurred – common to all cows with this phenotype. “We compared the genome of cattle with the “lineback” phenotype with that of the control cattle without this coat phenotype. And we found a region common to cows with the phenotype we are interested in on chromosome 29”, the scientist reveals. Unfortunately, this region was known for containing only one gene that was of no interest to this research. This gene isn’t expressed in the melanocytes. “We remained stuck at this stage for almost two years”, Carole Charlier remembers. 


It is quite by chance that this project resurfaced: “Keith Durkin, an Irish postdoctoral researcher who joined our laboratory, was working on another project aimed at establishing a catalogue of all the structural variants in the bovine genome”, the researcher continues. The structural variants, or structural polymorphisms, are all types of variations that can be observed within the genome of individuals of the same species such as deletions, duplications, translocations, inversions, and insertions of  DNA fragments. “To carry out his research, Keith used data produced by the laboratory over the past few years. This was genotyping data relating to the whole genome collected from the genome of 6000 to 7000 bovines from different breeds”, Carole Charlier points out. What the Irish researcher was actually looking for within this data were polymorphisms of a structural type referred to as copy-number variation, i.e., the deletion, duplication or multiplication of sections of DNA.


Out of the thousands of variants of this type that were revealed, Keith Durkin selected a number of them, either because of their large size, or because they contained genes that were potentially involved in interesting phenotypes. “Among these structural variants, one of them contained the KIT gene known for generating a particular coat phenotype when it is mutated”, the scientist reveals. “And based on this, we also realised that the genome of a certain number of animals in our database contained this duplicated gene and that they all shared the “lineback”coat phenotype”.