A dominant missense variant within LMBR1 related to equine polydactyly.

Abstract

Polydactyly was recorded before 100 BCE and attracted widespread interest because of its relationship to limb health and ancestral traits in horses. However, the underlying reasons for the development of polydactyly remain unclear. To search for polydactyly-related genes, we utilize a paternal half-sib family and screen for variants that match the mode of inheritance. Through this screening process, 77 variants in 65 genes are filtered. A missense variant (EqCab3.0 chr4:&#x2009;<107353368>&#x2009;A&#x2009;>&#x2009;G) (rs1138485164) in the 3rd exon of LMBR1 is identified as a source of amino acid sequence variation. Gene editing confirms that the variant down-regulates LMBR1expression, increases the proliferative viability of mutant cells, and inhibits apoptosis. This study suggests that LMBR1 might play a role in the development of polydactyly and that the variant detected in this study is related to polydactyly in horses. However, further research is needed to determine whether a direct relationship exists.