KDM2B is implicated in bovine lethal multi-organic developmental dysplasia.

Area of Science:

• Veterinary Genetics
• Developmental Biology
• Animal Breeding

Background:

• Romagnola cattle experienced an outbreak of a lethal congenital anomaly affecting multiple organs.
• The condition presents with facial deformities, ascites, and hepatic fibrosis in stillborn calves.
• Initial observations suggested autosomal monogenic recessive inheritance due to inbreeding to a single founder sire.

Purpose of the Study:

• To identify the genetic cause of the congenital anomaly in Romagnola cattle.
• To pinpoint the specific mutation responsible for the multi-organ developmental dysplasia.
• To understand the role of the identified gene in embryonic development.

Main Methods:

• Genome-wide association and identical by descent mapping to localize the mutation to a 1.2 Mb interval on BTA 17.
• Targeted DNA capture and massively parallel sequencing to analyze 24 genes within the critical region.
• Evaluation of homozygous non-synonymous coding sequence variants in affected calves.

Main Results:

• A missense mutation in the KDM2B gene (c.2503G>A) was identified, causing an amino acid exchange (p.D835N).
• This mutation occurred within a highly conserved domain of the KDM2B protein.
• Genetic analysis of multiple inbred cattle strongly supported the KDM2B mutation as the causative agent.

Conclusions:

• The congenital anomaly in Romagnola cattle is caused by a spontaneous mutation in the KDM2B gene.
• This finding demonstrates the critical role of KDM2B, a histone demethylase, in endo- and mesodermal organ development.
• The study provides valuable insights into the genetic basis of developmental disorders in cattle.