Identification of the causative gene for Simmental arachnomelia syndrome using a network-based disease gene prioritization approach

• Published in: PloS one 2013-05, Vol.8 (5), p.e64468-e64468
• Main Authors: Jiao, Shihui, Chu, Qin, Wang, Yachun, Xie, Zhenquan, Hou, Shiyu, Liu, Airong, Wu, Hongjun, Liu, Lin, Geng, Fanjun, Wang, Congyong, Qin, Chunhua, Tan, Rui, Huang, Xixia, Tan, Shixin, Wu, Meng, Xu, Xianzhou, Liu, Xuan, Yu, Ying, Zhang, Yuan
• Format: Article
• Language: English
• Subjects: Agriculture; Analysis; Animal sciences; Animals; Beef cattle; Biology; Bovidae; Breeding of animals; Cattle; Cattle Diseases - etiology; Cattle Diseases - genetics; Chromosomes, Mammalian - genetics; Dairy farms; Engineering; Gene deletion; Genes; Genetic aspects; Genomes; Genomics; Laboratories; Molybdenum; Mutation; Nuclear Proteins - genetics; Polymerase Chain Reaction; Polymorphism; Polymorphism, Restriction Fragment Length; Progeny; Proteins; Rankings; Restriction fragment length polymorphism; Skeletal system; Studies; Veterinary Science; Zoology
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0064468

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.