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.

Carole Charlier’s team has been working non-stop since the start of the academic year. In September, the Liègois team was approached by Holstein cattle breeders wanting to develop a test to detect the mutation responsible for a lethal disease in Holstein calves. Since then, the Liège team has achieved this objective and much more. ‘CDH, which stands for ‘cholesterol deficiency haplotype’, is a disease which leads to calves dying between three weeks and six months after birth’, explains Carole Charlier, project leader at the Animal Genomics Research Unit at the ULg GIGA. ‘Affected animals present severe diarrhoea, severe weight loss and almost no fat. Blood analyses shows an hypolipidaemic effect, particularly very low levels of cholesterol. There is currently no treatment for the illness’, she specifies. Given that the Holstein breed is the most widespread dairy breed in the world, you can imagine farmers’ distress faced with an illness such as this, which affects livestock production. This is particularly the case because CDH is not the only illness to affect the reproduction of Holstein cows (read the article Mutations that affect bovine fertility).

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.