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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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MLA
Ducro, Bart J., et al. “A Nonsense Mutation in B3GALNT2 Is Concordant with Hydrocephalus in Friesian Horses.” BMC GENOMICS, vol. 16, 2015, doi:10.1186/s12864-015-1936-z.
APA
Ducro, B. J., Schurink, A., Bastiaansen, J. W., Boegheim, I. J., van Steenbeek, F. G., Vos-Loohuis, M., … Leegwater, P. A. (2015). A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC GENOMICS, 16. https://doi.org/10.1186/s12864-015-1936-z
Chicago author-date
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. https://doi.org/10.1186/s12864-015-1936-z.
Chicago author-date (all authors)
Ducro, Bart J, Anouk Schurink, John WM Bastiaansen, Iris JM Boegheim, Frank G van Steenbeek, Manon Vos-Loohuis, Isaac J Nijman, Glen R Monroe, Ids Hellinga, Bert W Dibbits, Willem Back, and Peter AJ Leegwater. 2015. “A Nonsense Mutation in B3GALNT2 Is Concordant with Hydrocephalus in Friesian Horses.” BMC GENOMICS 16. doi:10.1186/s12864-015-1936-z.
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.
IEEE
[1]
B. J. Ducro et al., “A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses,” BMC GENOMICS, vol. 16, 2015.
@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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