Balancing selection of a frame-shift mutation in the MRC2 gene accounts for the outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle.
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.
Fasquelle
Corinne
C
Unit of Animal Genomics, GIGA-R, Department of Animal Sciences, Faculty of Veterinary Medicine, University of Liège, Liège, Belgium.
Sartelet
Arnaud
A
Li
Wanbo
W
Dive
Marc
M
Tamma
Nico
N
Michaux
Charles
C
Druet
Tom
T
Huijbers
Ivo J
IJ
Isacke
Clare M
CM
Coppieters
Wouter
W
Georges
Michel
M
Charlier
Carole
C
D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D001530:Belgium / Q000453:epidemiology; D002417:Cattle / Q000235:genetics*; D002418:Cattle Diseases / Q000453:epidemiology* / Q000235:genetics*; D018389:Codon, Nonsense / Q000235:genetics; D003198:Computer Simulation; D004196:Disease Outbreaks; D016368:Frameshift Mutation / Q000235:genetics*; D005786:Gene Expression Regulation; D006579:Heterozygote; D008562:Membrane Glycoproteins / Q000235:genetics*; D008969:Molecular Sequence Data; D016366:Open Reading Frames / Q000235:genetics; D009929:Organ Size; D009928:Organ Specificity; D019683:Penetrance; D020871:RNA Stability / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism; D012641:Selection, Genetic; D017384:Sequence Deletion
D018389:Codon, Nonsense; C408294:Endo180; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011975:Receptors, Mitogen