Endothelin receptor B polymorphism associated with lethal white foal syndrome in horses.

The research paper explores the relationship between a gene mutation in horses and the overo lethal white syndrome (OLWS), a hereditary condition that leads to the birth of almost completely white foals which usually die within Days due to complications linked to missing intestinal nerves.

Background of Overo Lethal White Syndrome (OLWS)

• The OLWS is a genetic disorder plaguing the offspring of American Paint Horse parents that bear overo coat-pattern lineage.
• The offspring impacted by this syndrome are almost entirely white and usually die within Days due to a health complication, intestinal aganglionosis, caused by missing nerves in the intestines.

Role of the Endothelin Receptor B (EDNRB) Gene

• In humans and rodents, similar conditions to the OLWS have been identified as being caused by mutations in the EDNRB gene.
• The EDNRB gene is understood to play a key role in guiding the development of neural crest cells into enteric ganglia and melanocytes.
• This research has identified that a polymorphism (a genetic variation) in the equine EDNRB gene is closely associated with OLWS.

Details of the Identified Polymorphism

• The identified genetic variation is a switch of an isoleucine (Ile) to a lysine (Lys) residue at the 118th codon. This modification occurs within the first transmembrane domain of the seven-transmembrane domain G-protein-coupled receptor protein.
• The research found all the 22 OLWS-impacted foals studied were homozygous (having two identical alleles for the same trait) for the Lys118 EDNRB allele, while all their parents were heterozygous (two different alleles for the same trait).
• All but one of the parent horses exhibited an overo white body-spot phenotype.
• In comparison, solid-colored horses of other breeds that were used as controls were found to be homozygous for the Ile118 EDNRB allele, thus not showing any sign of the OLWS disease.

Implications of the Findings

• The findings offer a molecular definition for the genesis of OLWS in Paint Horses.
• It also allows the development of a genetic test to detect the presence of the Lys118 EDNRB allele, which would be useful for mitigating potential OLWS cases before they occur.
• Besides, this research enhances our understanding regarding the factors that determine coat color patterns in horses.