title: Identification of the causative gene for Simmental arachnomelia syndrome using a network-based disease gene prioritization approach.
abstract: Arachnomelia syndrome (AS), mainly found in Brown Swiss and Simmental cattle, is a congenital lethal genetic malformation of the skeletal system. In this study, a network-based disease gene prioritization approach was implemented to rank genes in the previously reported ∼7 Mb region on chromosome 23 associated with AS in Simmental cattle. The top 6 ranked candidate genes were sequenced in four German Simmental bulls, one known AS-carrier ROMEL and a pooled sample of three known non-carriers (BOSSAG, RIFURT and HIRMER). Two suspicious mutations located in coding regions, a mis-sense mutation c.1303G>A in the bystin-like (BYSL) gene and a 2-bp deletion mutation c.1224_1225delCA in the molybdenum cofactor synthesis step 1 (MOCS1) gene were detected. Bioinformatic analysis revealed that the mutation in MOCS1 was more likely to be the causative mutation. Screening the c.1224_1225delCA site in 383 individuals from 12 cattle breeds/lines, we found that only the bull ROMEL and his 12 confirmed progeny carried the mutation. Thus, our results confirm the conclusion of Buitkamp et al. that the 2-bp deletion mutation c.1224_1225delCA in exon 11 of the MOCS1 gene is causative for AS in Simmental cattle. Furthermore, a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was developed to detect the causative mutation.
authors.affiliation: Key Laboratory of Agricultural Animal and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, China.
authors.forename: Shihui
authors.initials: S
authors.lastname: Jiao
authors.forename: Qin
authors.initials: Q
authors.lastname: Chu
authors.forename: Yachun
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhenquan
authors.initials: Z
authors.lastname: Xie
authors.forename: Shiyu
authors.initials: S
authors.lastname: Hou
authors.forename: Airong
authors.initials: A
authors.lastname: Liu
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Fanjun
authors.initials: F
authors.lastname: Geng
authors.forename: Congyong
authors.initials: C
authors.lastname: Wang
authors.forename: Chunhua
authors.initials: C
authors.lastname: Qin
authors.forename: Rui
authors.initials: R
authors.lastname: Tan
authors.forename: Xixia
authors.initials: X
authors.lastname: Huang
authors.forename: Shixin
authors.initials: S
authors.lastname: Tan
authors.forename: Meng
authors.initials: M
authors.lastname: Wu
authors.forename: Xianzhou
authors.initials: X
authors.lastname: Xu
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002417:Cattle; D002418:Cattle Diseases / Q000209:etiology / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D009687:Nuclear Proteins