Identifying cholesterol deficiency in Holstein cattle
Cholesterol deficiency is a genetic defect which causes the early death of young Holstein cattle. To prevent more animals being affected by this disease, there was a need to detect which animals carried the genetic mutation responsible for it, in order to avoid using them for reproduction. Carole Charlier, project head at the Animal Genomics Research Unit at the ULg GIGA, and her team, identified this mutation and have developed a test to detect animals carrying it. The culprit is the APOB gene, which gives rise to an ‘abnormal’ protein.
A unique database in Europe
To prevent Holstein cows giving birth to diseased calves, the breeders needed to find the mutation responsible for this illness in order to avoid using animals who carry that mutation for reproduction. ‘It was a German team who described the illness and the same team presented the location of the mutation responsible for this illness, at a seminar in July’, continues Carole Charlier. ‘They had localised this mutation at chromosome 11 but had not yet identified it. Based on this, they had developed an indirect haplotype test, in other words, a test which made it possible to identify the part of the chromosome which should carry the mutation. The test is not 100% reliable but it is useful to identify animals who may potentially carry the mutation’. Once they had this information, Carole Charlier’s team sought to identify the mutation responsible for CDH. To do so, they had one key tool: a database, generated be Wouter Coppieters and his team within GIGA’s genomic platform, covering the sequencing of 750 complete genomes from Holstein cows. ‘This database had been developed over the last two years as part of the DAMONA project led by Professor Michel Georges and funded by an ERC Advanced Grant’, clarifies Charlier. Based on a list of reproductive bulls likely to carry the mutation responsible for CDH, the researchers were able to identify four bulls who formed part of the DAMONA database. They then analysed the part of chromosome 11 where the German team had localised the mutation in question. ‘We didn’t find anything at that location’, says Charlier. ‘But one million base pairs from this location is the apolipoprotein B gene (APOB). In humans, we know that ‘loss of function’ type mutations of this gene provoke similar symptoms to those observed in calves with CDH’, explains Charlier. Could there be a mutation in the APOB gene which could explain the appearance of the cholesterol deficiency in Holstein cattle? This is what the researchers aimed to find out.