A nonsense mutation causes hydrocephalus in Friesian horses

A. Schurink; B.J. Ducro; J.W.M. Bastiaansen; I.J.M. Boegheim; F.G. van Steenbeek; M. Vos-Loohuis; I.J. Nijman; G.R. Monroe; I. Hellinga; B.W. Dibbits; W. Back; P.A.J. Leegwater

Abstract

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 identify the causal mutation for hydrocephalus in Friesian horses, as it will help in understanding its aetiology and allow selection against the disease allele using a DNA test. Genotypes were obtained using the Illumina® EquineSNP50 Genotyping BeadChip, where 29,270 SNPs remained after quality control. Significance level of genotype differences between cases (n = 13) and controls (n = 69) per SNP was determined with a χ2-test using the ccfast function in the GenABEL package in R. One strongly associated region was found and examined to identify overlapping regions of homozygosity between cases. Next generation DNA sequence analysis was performed of gene exons in the identified region on 4 cases and 6 controls. A genome-wide association study of hydrocephalus indicated the involvement of a region on ECA1 (P <1.68×10-6). All cases, and none of the controls, carried 2 copies of a 0.58 Mb haplotype. Next generation DNA sequence analysis revealed a nonsense mutation that was identical to a mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All available cases and none of the controls were homozygous for the mutation. 32 controls were heterozygotes of which 17 were dams of cases and 36 controls were homozygous for the normal allele. Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation is responsible for hydrocephalus in Friesian horses and classifies the phenotype as a muscular dystrophy-dystroglycanopathy. Currently, Friesian horses are tested for the presence of the disease allele, which allows selection against this allele and thereby reduction in losses and suffering caused by hydrocephalus in the Friesian horse population.

Original language	English
Publication status	Published - Jul 2015
Event	11th International Equine Gene Mapping Workshop - Hannover, Germany Duration: 22 Jul 2015 → 25 Jul 2015

Conference

Conference	11th International Equine Gene Mapping Workshop
Country/Territory	Germany
City	Hannover
Period	22/07/15 → 25/07/15

Keywords

hydrocephalus
friesian horses
mutation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

https://edepot.wur.nl/377940

Cite this

Schurink, A., Ducro, B. J., Bastiaansen, J. W. M., Boegheim, I. J. M., van Steenbeek, F. G., Vos-Loohuis, M., Nijman, I. J., Monroe, G. R., Hellinga, I., Dibbits, B. W., Back, W., & Leegwater, P. A. J. (2015). A nonsense mutation causes hydrocephalus in Friesian horses. Abstract from 11th International Equine Gene Mapping Workshop, Hannover, Germany. https://edepot.wur.nl/377940

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title = "A nonsense mutation causes hydrocephalus in Friesian horses",

abstract = "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 identify the causal mutation for hydrocephalus in Friesian horses, as it will help in understanding its aetiology and allow selection against the disease allele using a DNA test. Genotypes were obtained using the Illumina{\textregistered} EquineSNP50 Genotyping BeadChip, where 29,270 SNPs remained after quality control. Significance level of genotype differences between cases (n = 13) and controls (n = 69) per SNP was determined with a χ2-test using the ccfast function in the GenABEL package in R. One strongly associated region was found and examined to identify overlapping regions of homozygosity between cases. Next generation DNA sequence analysis was performed of gene exons in the identified region on 4 cases and 6 controls. A genome-wide association study of hydrocephalus indicated the involvement of a region on ECA1 (P <1.68×10-6). All cases, and none of the controls, carried 2 copies of a 0.58 Mb haplotype. Next generation DNA sequence analysis revealed a nonsense mutation that was identical to a mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All available cases and none of the controls were homozygous for the mutation. 32 controls were heterozygotes of which 17 were dams of cases and 36 controls were homozygous for the normal allele. Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation is responsible for hydrocephalus in Friesian horses and classifies the phenotype as a muscular dystrophy-dystroglycanopathy. Currently, Friesian horses are tested for the presence of the disease allele, which allows selection against this allele and thereby reduction in losses and suffering caused by hydrocephalus in the Friesian horse population.",

keywords = "hydrocephalus, friesian horses, mutation",

author = "A. Schurink and B.J. Ducro and J.W.M. Bastiaansen and I.J.M. Boegheim and {van Steenbeek}, F.G. and M. Vos-Loohuis and I.J. Nijman and G.R. Monroe and I. Hellinga and B.W. Dibbits and W. Back and P.A.J. Leegwater",

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note = "11th International Equine Gene Mapping Workshop ; Conference date: 22-07-2015 Through 25-07-2015",

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T1 - A nonsense mutation causes hydrocephalus in Friesian horses

AU - Schurink, A.

AU - Ducro, B.J.

AU - Bastiaansen, J.W.M.

AU - Boegheim, I.J.M.

AU - van Steenbeek, F.G.

AU - Vos-Loohuis, M.

AU - Nijman, I.J.

AU - Monroe, G.R.

AU - Hellinga, I.

AU - Dibbits, B.W.

AU - Back, W.

AU - Leegwater, P.A.J.

PY - 2015/7

Y1 - 2015/7

N2 - 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 identify the causal mutation for hydrocephalus in Friesian horses, as it will help in understanding its aetiology and allow selection against the disease allele using a DNA test. Genotypes were obtained using the Illumina® EquineSNP50 Genotyping BeadChip, where 29,270 SNPs remained after quality control. Significance level of genotype differences between cases (n = 13) and controls (n = 69) per SNP was determined with a χ2-test using the ccfast function in the GenABEL package in R. One strongly associated region was found and examined to identify overlapping regions of homozygosity between cases. Next generation DNA sequence analysis was performed of gene exons in the identified region on 4 cases and 6 controls. A genome-wide association study of hydrocephalus indicated the involvement of a region on ECA1 (P <1.68×10-6). All cases, and none of the controls, carried 2 copies of a 0.58 Mb haplotype. Next generation DNA sequence analysis revealed a nonsense mutation that was identical to a mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All available cases and none of the controls were homozygous for the mutation. 32 controls were heterozygotes of which 17 were dams of cases and 36 controls were homozygous for the normal allele. Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation is responsible for hydrocephalus in Friesian horses and classifies the phenotype as a muscular dystrophy-dystroglycanopathy. Currently, Friesian horses are tested for the presence of the disease allele, which allows selection against this allele and thereby reduction in losses and suffering caused by hydrocephalus in the Friesian horse population.

AB - 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 identify the causal mutation for hydrocephalus in Friesian horses, as it will help in understanding its aetiology and allow selection against the disease allele using a DNA test. Genotypes were obtained using the Illumina® EquineSNP50 Genotyping BeadChip, where 29,270 SNPs remained after quality control. Significance level of genotype differences between cases (n = 13) and controls (n = 69) per SNP was determined with a χ2-test using the ccfast function in the GenABEL package in R. One strongly associated region was found and examined to identify overlapping regions of homozygosity between cases. Next generation DNA sequence analysis was performed of gene exons in the identified region on 4 cases and 6 controls. A genome-wide association study of hydrocephalus indicated the involvement of a region on ECA1 (P <1.68×10-6). All cases, and none of the controls, carried 2 copies of a 0.58 Mb haplotype. Next generation DNA sequence analysis revealed a nonsense mutation that was identical to a mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus. All available cases and none of the controls were homozygous for the mutation. 32 controls were heterozygotes of which 17 were dams of cases and 36 controls were homozygous for the normal allele. Hydrocephalus in Friesian horses has an autosomal recessive mode of inheritance. A nonsense mutation is responsible for hydrocephalus in Friesian horses and classifies the phenotype as a muscular dystrophy-dystroglycanopathy. Currently, Friesian horses are tested for the presence of the disease allele, which allows selection against this allele and thereby reduction in losses and suffering caused by hydrocephalus in the Friesian horse population.

KW - hydrocephalus

KW - friesian horses

KW - mutation

M3 - Abstract

T2 - 11th International Equine Gene Mapping Workshop

Y2 - 22 July 2015 through 25 July 2015

ER -