A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. (December 2015)

• Record Type: Journal Article
• Authors: Ducro, Bart; Schurink, Anouk; Bastiaansen, John; Boegheim, Iris; Steenbeek, Frank; Vos-Loohuis, Manon; Nijman, Isaac; Monroe, Glen; Hellinga, Ids; Dibbits, Bert; Back, Willem; Leegwater, Peter
• Is Part Of: BMC genomics. Volume 16:Number 1(2015)
• Page Start: 1
• Page End: 9
• Publication Date: 2015-12
• Subjects: Hydrocephalus -- B3GALNT2 -- Genome-wide association study -- Next generation sequencing -- Friesian horse -- Muscular dystrophy; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/s12864-015-1936-z
• Languages: English
• ISSNs: 1471-2164

Abstract

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 × 10−6 ). 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 aB3GALNT2 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* inB3GALNT2 (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.