Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle

• Published in: PLoS genetics Vol. 5; no. 9; p. e1000666
• Main Authors: Fasquelle, Corinne, Sartelet, Arnaud, Li, Wanbo, Dive, Marc, Tamma, Nico, Michaux, Charles, Druet, Tom, Huijbers, Ivo J., Isacke, Clare M., Coppieters, Wouter, Georges, Michel, Charlier, Carole
• Format: Journal Article Web Resource
• Language: English
• Published: United States Public Library of Science 01.09.2009; Public Library of Science (PLoS)
• Subjects: Animals; Base Pairing - genetics; Base Sequence; Belgium - epidemiology; Cattle; Cattle - genetics; Cattle Diseases - epidemiology; Cattle Diseases - genetics; Cell receptors; Codon, Nonsense - genetics; Computer Simulation; Disease Outbreaks; Diseases; Frameshift Mutation - genetics; Gene Expression Regulation; Gene mutations; Genes; Genetic aspects; Genetics; Genetics & genetic processes; Genetics and Genomics; Genetics and Genomics/Animal Genetics; Genetics and Genomics/Comparative Genomics; Genetics and Genomics/Disease Models; Génétique & processus génétiques; Health aspects; Heterozygote; Life sciences; Membrane Glycoproteins - genetics; Molecular Sequence Data; Mutation; Open Reading Frames - genetics; Organ Size; Organ Specificity; Penetrance; Physiological aspects; Receptors, Mitogen - genetics; Receptors, Mitogen - metabolism; RNA Stability - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; Sciences du vivant; Selection, Genetic; Sequence Deletion; Belgium; United Kingdom
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1000666

We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed.