PMID- 26452345 OWN - NLM STAT- MEDLINE DCOM- 20160622 LR - 20181113 IS - 1471-2164 (Electronic) IS - 1471-2164 (Linking) VI - 16 DP - 2015 Oct 9 TI - A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. PG - 761 LID - 10.1186/s12864-015-1936-z [doi] LID - 761 AB - 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. FAU - Ducro, Bart J AU - Ducro BJ AD - Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. bart.ducro@wur.nl. FAU - Schurink, Anouk AU - Schurink A AD - Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. anouk3.schurink@wur.nl. FAU - Bastiaansen, John W M AU - Bastiaansen JW AD - Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. john.bastiaansen@wur.nl. FAU - Boegheim, Iris J M AU - Boegheim IJ AD - Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80154, 3508 TD, Utrecht, The Netherlands. i.j.m.boegheim@students.uu.nl. FAU - van Steenbeek, Frank G AU - van Steenbeek FG AD - Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80154, 3508 TD, Utrecht, The Netherlands. f.g.vansteenbeek@uu.nl. FAU - Vos-Loohuis, Manon AU - Vos-Loohuis M AD - Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80154, 3508 TD, Utrecht, The Netherlands. m.vos@uu.nl. FAU - Nijman, Isaac J AU - Nijman IJ AD - Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands. inijman@umcutrecht.nl. FAU - Monroe, Glen R AU - Monroe GR AD - Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands. g.monroe@umcutrecht.nl. FAU - Hellinga, Ids AU - Hellinga I AD - Koninklijke Vereniging "Het Friesch Paarden-Stamboek", PO Box 624, 9200 AP, Drachten, The Netherlands. idshellinga@kfps.nl. FAU - Dibbits, Bert W AU - Dibbits BW AD - Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. bert.dibbits@wur.nl. FAU - Back, Willem AU - Back W AD - Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112-114, 3584 CM, Utrecht, The Netherlands. W.Back@uu.nl. AD - Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium. W.Back@uu.nl. FAU - Leegwater, Peter A J AU - Leegwater PA AD - Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, PO Box 80154, 3508 TD, Utrecht, The Netherlands. P.A.J.Leegwater@uu.nl. LA - eng PT - Journal Article DEP - 20151009 PL - England TA - BMC Genomics JT - BMC genomics JID - 100965258 RN - 0 (Codon, Nonsense) RN - EC 2.4.1.- (N-Acetylgalactosaminyltransferases) SB - IM MH - Alleles MH - Animals MH - Breeding MH - Codon, Nonsense/*genetics MH - Exons MH - Female MH - Genome-Wide Association Study MH - Horse Diseases/*genetics MH - Horses MH - Humans MH - Hydrocephalus/*genetics/pathology MH - Inbreeding MH - N-Acetylgalactosaminyltransferases/*genetics MH - Polymorphism, Single Nucleotide MH - Pregnancy PMC - PMC4600337 EDAT- 2015/10/11 06:00 MHDA- 2016/06/23 06:00 PMCR- 2015/10/09 CRDT- 2015/10/11 06:00 PHST- 2015/06/05 00:00 [received] PHST- 2015/09/21 00:00 [accepted] PHST- 2015/10/11 06:00 [entrez] PHST- 2015/10/11 06:00 [pubmed] PHST- 2016/06/23 06:00 [medline] PHST- 2015/10/09 00:00 [pmc-release] AID - 10.1186/s12864-015-1936-z [pii] AID - 1936 [pii] AID - 10.1186/s12864-015-1936-z [doi] PST - epublish SO - BMC Genomics. 2015 Oct 9;16:761. doi: 10.1186/s12864-015-1936-z.