title: Deletion of Indian hedgehog gene causes dominant semi-lethal Creeper trait in chicken.
abstract: The Creeper trait, a classical monogenic phenotype of chicken, is controlled by a dominant semi-lethal gene. This trait has been widely cited in the genetics and molecular biology textbooks for illustrating autosomal dominant semi-lethal inheritance over decades. However, the genetic basis of the Creeper trait remains unknown. Here we have utilized ultra-deep sequencing and extensive analysis for targeting causative mutation controlling the Creeper trait. Our results indicated that the deletion of Indian hedgehog (IHH) gene was only found in the whole-genome sequencing data of lethal embryos and Creeper chickens. Large scale segregation analysis demonstrated that the deletion of IHH was fully linked with early embryonic death and the Creeper trait. Expression analysis showed a much lower expression of IHH in Creeper than wild-type chickens. We therefore suggest the deletion of IHH to be the causative mutation for the Creeper trait in chicken. Our findings unravel the genetic basis of the longstanding Creeper phenotype mystery in chicken as the same gene also underlies bone dysplasia in human and mouse, and thus highlight the significance of IHH in animal development and human haploinsufficiency disorders.
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Sihua
authors.initials: S
authors.lastname: Jin
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Yi
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Li
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lian
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Jiangxia
authors.initials: J
authors.lastname: Zheng
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Xu
authors.affiliation: Rural Energy Management Station of Guizhou Province, Guiyang, 550001, China.
authors.forename: Rengang
authors.initials: R
authors.lastname: Jiao
authors.affiliation: Livestock Genetic Resources Management Station of Guizhou Province, Guiyang, 550001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Gong
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Zhuocheng
authors.initials: Z
authors.lastname: Hou
authors.affiliation: National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, China Agricultural University, Beijing 100193, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Yang
mesh_terms: D000818:Animals; D002645:Chickens / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005804:Genes, Lethal; D053823:Hedgehog Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation; D010641:Phenotype
chemical_list: D053823:Hedgehog Proteins