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 × 10−6). 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 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1936-z) contains supplementary material, which is available to authorized users.
Highlights
Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams
A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses, which has an autosomal recessive mode of inheritance
A genome-wide association study and homozygosity mapping identified a region on ECA1 highly associated with hydrocephalus
Summary
Hydrocephalus in Friesian horses is a developmental disorder that often results in stillbirth of affected foals and dystocia in dams. Hydrocephalus is defined as “an active distension of the ventricular system of the brain resulting from inadequate passage of cerebrospinal fluid (CSF) from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation” [11]. Hydrocephalus can be internal or external, that is an accumulation of CSF respectively within or outside the ventricles of the brain. The most likely cause of hydrocephalus in Friesian horses, based on the findings from the examinations of these 4 foals, was an abnormal narrowing (stenosis) of the jugular foramen, suggesting “a communicative (external) hydrocephalus with a diminished absorption of cerebrospinal fluid into the systemic circulation at the venous sinuses due to a distorted, nonfunctional jugular foramen” [6]. The incidence of hydrocephalus was 3.0 % in a population of 608 deformed fetuses or new-born foals, mostly Thoroughbreds, that were submitted for necropsy [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
