When cattle chromosomes get tangled: detecting genetic defects to better prevent them

Interchromosomal rearrangements are exchanges of genetic material between two chromosomes that are not part of the same pair. They usually appear at the time gametes are formed. In the vast majority of cases, such anomalies lead to early death of the embryo. In other cases, chromosomal rearrangements can have severe pathological effects, as has been shown in humans. All animals, whatever their sex or race, may be affected, whether or not they are breeding stock. The widespread use of animal insemination causes bovine populations to be particularly at risk from the hazards of mass distribution of the semen of healthy carrier sires not affected themselves by such mutations. However, up to now, no large-scale analysis has been done to study the prevelance of interchromosomal rearrangements, their origins and their impact on animals and the cattle sector.

Genetic analysis out on 5571 bulls and their 2 million offspring, from 15 breeds

The study examined 5571 bulls from 15 breeds for a total of more than two (2) million individual progeny. For their analysis, the geneticists used 50,000 genetic variants that set out the genome of each offspring. These markers are routinely used as part of genomic evaluation of breeding stock. The researchers screened billions of possible combinations of pairs of different chromosome markers to see if there were any instances of preferential transmission that would indicate the existence of a interchromosomal rearrangement. They also estimated the effects such anomalies have on the health, survival and reproductive traits of offspring using the millions of data points about their characteristics recorded in French animal breeding databases.

1 sire out of every 450 may be a carrier of such chromosomal defects

Their work made it possible to identify 12 interchromosomal rearrangements, some of which had never before been described in bovines. Such defects would affect about 1 in every 450 bulls. Transgenerational tracking of rearranged chromosomes revealed that most often they had been the result of spontaneous rearrangements during gamete formation in the sires (10 times out of 12). Ten of the bulls with interchromosomal rearrangements had been classified among the least fertile of their race, and the progeny of one of them showed a record-breaking juvenile mortality rate, with 44% of the heifers dying before the age of one. In most cases, analysis of the animal breeding data of those offspring that had inherited the anomaly showed stunted growth and lower fertility in comparison to those heifers with normal chromosomes from the same sire. The researchers estimated that, on average, one or two insemination sires would be affected by such defects each year in France. In each case, dissemination of their semen would cost more than EUR 1 million due to excess mortality and decreased fertility and productivity in their offspring. To solve that problem, these scientists have recommended wide-spread use of prevention methods such as karotyping bulls, i.e. studying the structure and number of their chromosomes. They highlighed the importance of also using the approach developed during this study, i.e. using genetic marker data, to contribute to systematic, wide-spread screening for chromosomal rearrangements. This method is readily applicable to any animal or plant popuation that benefits from large sets of genotype data, with direct agricultural applications.