The Genetic Origin of Fragile Foal Syndrome

A genetic study of a Thoroughbred stallion who had a major influence on German horse breeding at the beginning of the last century sheds light on the origin of a fatal genetic disorder known as fragile foal syndrome.   Fragile Foal Syndrome is a fatal genetic disorder in warm-blooded horses characterized by extremely fragile skin and unstable connective tissue from birth. In humans, the disease is known as Ehlers-Danlos syndrome type VI. The disease itself is not new. Although it likely originated in the mid-18th century, the syndrome was not identified until the early 21st century; it was described through clinical cases in 2011 and 2015, and the responsible gene was identified in 2012. Since then, all breeding animals have been systematically tested for the genetic defect. The gene involved, PLOD1, normally ensures that collagen molecules in the skin and connective tissue form a stable network. A mutation in the PLOD1 gene prevents the cross-linking of collagen strands, which is necessary for its stability. By tracing the disease across several horse bloodlines (approximately 2,000 horses tested and their pedigree records studied), particularly German ones, the Vereinigte Informationssysteme Tierhaltung (IT Solutions for Animal Production) in Verden (2019) was able to trace the origin of the genetic mutation to a specific horse. The culprit, the English Thoroughbred stallion Dark Ronald XX (1905–1928)—or his sire, Bay Ronald XX—had likely passed the genetic defect on to his offspring. Dark Ronald XX was an important Thoroughbred stallion who had a major influence on German horse breeding. He died of colic at the University of Halle’s veterinary clinic in 1928, and part of his remains was preserved in one of the natural science collections at Martin Luther University Halle-Wittenberg. This presented an opportunity for scientists, who were able to sequence his DNA—now over 100 years old—and check for the presence of the PLOD1 mutation. And this new study conducted by the University of Göttingen calls into question Dark Ronald XX’s role in the spread of the condition. It turns out, in fact, that he was not a carrier of the PLOD1 mutation and was therefore not the source of this genetic defect; rather, it was a Hanoverian stallion born in 1861. Stay tuned for further developments.