A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horsesReportar como inadecuado




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BMC Genomics

, 16:761

Non-human and non-rodent vertebrate genomics

Abstract

BackgroundHydrocephalus 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.

ResultsA 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 × 10. Next generation DNA sequence analysis of 4 cases and 6 controls of gene exons within the region revealed a mutation in β-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.

ConclusionsHydrocephalus 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.

KeywordsHydrocephalus B3GALNT2 Genome-wide association study Next generation sequencing Friesian horse Muscular dystrophy AbbreviationsECAEquus caballus

CSFCerebrospinal fluid

OMIMOnline Mendelian Inheritance in Man

OMIAOnline Mendelian Inheritance in Animals

B3GALNT2β-1,3-N-acetylgalactosaminyltransferase 2

Bart J. Ducro and Anouk Schurink contributed equally to this work.

Electronic supplementary materialThe online version of this article doi:10.1186-s12864-015-1936-z contains supplementary material, which is available to authorized users.

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Autor: Bart J. Ducro - Anouk Schurink - John W. M. Bastiaansen - Iris J. M. Boegheim - Frank G. van Steenbeek - Manon Vos-Lo

Fuente: https://link.springer.com/



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