Combined deletions of and cause chondrodystrophy and embryonic lethality in the Creeper chicken.

The Creeper () chicken is characterized by chondrodystrophy in /+ heterozygotes and embryonic lethality in / homozygotes. However, the genes underlying the phenotypes have not been fully known. Here, we show that a 25 kb deletion on chromosome 7, which contains the Indian hedgehog () and non-homologous end-joining factor 1 () genes, is responsible for the trait in Japanese bantam chickens. is essential for chondrocyte maturation and is downregulated in the embryos and completely lost in the / embryos. This indicates that chondrodystrophy is caused by the loss of and that chondrocyte maturation is delayed in / heterozygotes. The / homozygotes exhibit impaired DNA double-strand break (DSB) repair due to the loss of , resulting in DSB accumulation in the vascular and nervous systems, which leads to apoptosis and early embryonic death.