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A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses

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Abstract
Background: Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. The occurrence is probably related to a founder effect and inbreeding in the population. The aim of our study was to find genomic associations, to investigate the mode of inheritance, to allow a DNA test for hydrocephalus in Friesian horses to be developed. In case of a monogenic inheritance we aimed to identify the causal mutation. Results: A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement of a region on ECA1 (P < 1.68 x 10(-6)). Next generation DNA sequence analysis of 4 cases and 6 controls of gene exons within the region revealed a mutation in beta-1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2) as the likely cause of hydrocephalus in Friesian horses. The nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All 16 available cases and none of the controls were homozygous for the mutation, and all 17 obligate carriers (= dams of cases) were heterozygous. A random sample of the Friesian horse population (n = 865) was tested for the mutation in a commercial laboratory. One-hundred and forty-seven horses were carrier and 718 horses were homozygous for the normal allele; the estimated allele frequency in the Friesian horse population is 0.085. Conclusions: Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* in B3GALNT2 (1: 75,859,296-75,909,376) is concordant with hydrocephalus in Friesian horses. Application of a DNA test in the breeding programme will reduce the losses caused by hydrocephalus in the Friesian horse population.
Keywords
CALF, FOALS, SNP, GENE, Hydrocephalus, B3GALNT2, Genome-wide association study, Next generation sequencing, Friesian horse, Muscular dystrophy, CONGENITAL MUSCULAR-DYSTROPHY, GENOMIC ENRICHMENT, DYSTROGLYCAN

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Chicago
Ducro, Bart J, Anouk Schurink, John WM Bastiaansen, Iris JM Boegheim, Frank G van Steenbeek, Manon Vos-Loohuis, Isaac J Nijman, et al. 2015. “A Nonsense Mutation in B3GALNT2 Is Concordant with Hydrocephalus in Friesian Horses.” Bmc Genomics 16.
APA
Ducro, B. J., Schurink, A., Bastiaansen, J. W., Boegheim, I. J., van Steenbeek, F. G., Vos-Loohuis, M., Nijman, I. J., et al. (2015). A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC GENOMICS, 16.
Vancouver
1.
Ducro BJ, Schurink A, Bastiaansen JW, Boegheim IJ, van Steenbeek FG, Vos-Loohuis M, et al. A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC GENOMICS. 2015;16.
MLA
Ducro, Bart J et al. “A Nonsense Mutation in B3GALNT2 Is Concordant with Hydrocephalus in Friesian Horses.” BMC GENOMICS 16 (2015): n. pag. Print.
@article{7096818,
  abstract     = {Background: Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. The occurrence is probably related to a founder effect and inbreeding in the population. The aim of our study was to find genomic associations, to investigate the mode of inheritance, to allow a DNA test for hydrocephalus in Friesian horses to be developed. In case of a monogenic inheritance we aimed to identify the causal mutation. 
Results: A genome-wide association study of hydrocephalus in 13 cases and 69 controls using 29,720 SNPs indicated the involvement of a region on ECA1 (P < 1.68 x 10(-6)). Next generation DNA sequence analysis of 4 cases and 6 controls of gene exons within the region revealed a mutation in beta-1,3-N-acetylgalactosaminyltransferase 2 (B3GALNT2) as the likely cause of hydrocephalus in Friesian horses. The nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* was identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All 16 available cases and none of the controls were homozygous for the mutation, and all 17 obligate carriers (= dams of cases) were heterozygous. A random sample of the Friesian horse population (n = 865) was tested for the mutation in a commercial laboratory. One-hundred and forty-seven horses were carrier and 718 horses were homozygous for the normal allele; the estimated allele frequency in the Friesian horse population is 0.085. 
Conclusions: Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation XM_001491545 c.1423C>T corresponding to XP_001491595 p.Gln475* in B3GALNT2 (1: 75,859,296-75,909,376) is concordant with hydrocephalus in Friesian horses. Application of a DNA test in the breeding programme will reduce the losses caused by hydrocephalus in the Friesian horse population.},
  articleno    = {761},
  author       = {Ducro, Bart J and Schurink, Anouk and Bastiaansen, John WM and Boegheim, Iris JM and van Steenbeek, Frank G and Vos-Loohuis, Manon and Nijman, Isaac J and Monroe, Glen R and Hellinga, Ids and Dibbits, Bert W and Back, Willem and Leegwater, Peter AJ},
  issn         = {1471-2164},
  journal      = {BMC GENOMICS},
  keywords     = {CALF,FOALS,SNP,GENE,Hydrocephalus,B3GALNT2,Genome-wide association study,Next generation sequencing,Friesian horse,Muscular dystrophy,CONGENITAL MUSCULAR-DYSTROPHY,GENOMIC ENRICHMENT,DYSTROGLYCAN},
  language     = {eng},
  pages        = {9},
  title        = {A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses},
  url          = {http://dx.doi.org/10.1186/s12864-015-1936-z},
  volume       = {16},
  year         = {2015},
}

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