FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / BMC Genomics / A nonsense mutation in B3GALNT2 is concordant with hydroceph...
BMC genomics2015; 16; 761; doi: 10.1186/s12864-015-1936-z

A nonsense mutation in B3GALNT2 is concordant with 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 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 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.
Get Full Text
Publication Date: 2015-10-09 PubMed ID: 26452345PubMed Central: PMC4600337DOI: 10.1186/s12864-015-1936-zGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigated the cause of hydrocephalus, a developmental disorder, in Friesian horses, pinpointing a specific mutation in the B3GALNT2 gene as the likely cause. The study also developed a DNA test to detect this mutation, thus enabling preventative measures in breeding programs.

Objective of Research

  • The main purpose of this study was to find genomic associations of hydrocephalus, a developmental issue leading to stillbirth in Friesian horses, and to investigate its inheritance pattern.
  • Consequently, the aim was to develop a DNA test for hydrocephalus if a monogenic inheritance was discovered, and identify the causing mutation.

Research Methodology

  • The researchers conducted a genome-wide association study with 13 cases and 69 controls using 29,720 SNPs. The results indicated the involvement of a region on ECA1.
  • Next, next-generation DNA sequence analysis was conducted on 4 cases and 6 controls within this region. It revealed a B3GALNT2 mutation as probable cause for hydrocephalus in Friesian horses.
  • This identified mutation XM_001491545 c.1423C>T was found to be identical to a B3GALNT2 mutation identified in a human case of muscular dystrophy-dystroglycanopathy with hydrocephalus.

Research Findings

  • The study found all 16 available cases were homozygous for the mutation, and none of the controls were. All 17 dams of these cases were heterozygous.
  • The research also sampled the Friesian horse population (865 horses), in a commercial laboratory. One-hundred and forty-seven horses were carriers and 718 horses were homozygous for the normal allele. The estimated allele frequency in the Friesian horse population was calculated as 0.085.

Conclusion of the Study

  • The study concluded that hydrocephalus in Friesian horses is autosomally recessive. The identified nonsense mutation XM_001491545 c.1423C>T in B3GALNT2 is concordant with hydrocephalus in Friesian horses.
  • The study also developed and proposed the application of a DNA test in the breeding programmes. This measure is predicted to reduce losses caused by hydrocephalus in the Friesian horse population.

Cite This Article

APA
Ducro BJ, Schurink A, Bastiaansen JW, Boegheim IJ, van Steenbeek FG, Vos-Loohuis M, Nijman IJ, Monroe GR, Hellinga I, Dibbits BW, Back W, Leegwater PA. (2015). A nonsense mutation in B3GALNT2 is concordant with hydrocephalus in Friesian horses. BMC Genomics, 16, 761. https://doi.org/10.1186/s12864-015-1936-z

Publication

BMC genomics
ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 16
Pages: 761

Researcher Affiliations

Ducro, Bart J
  • Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. bart.ducro@wur.nl.
Schurink, Anouk
  • Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. anouk3.schurink@wur.nl.
Bastiaansen, John W M
  • Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. john.bastiaansen@wur.nl.
Boegheim, Iris J M
  • 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.
van Steenbeek, Frank G
  • 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.
Vos-Loohuis, Manon
  • 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.
Nijman, Isaac J
  • Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands. inijman@umcutrecht.nl.
Monroe, Glen R
  • Department of Medical Genetics, University Medical Center Utrecht, PO Box 85090, 3508 AB, Utrecht, The Netherlands. g.monroe@umcutrecht.nl.
Hellinga, Ids
  • Koninklijke Vereniging "Het Friesch Paarden-Stamboek", PO Box 624, 9200 AP, Drachten, The Netherlands. idshellinga@kfps.nl.
Dibbits, Bert W
  • Animal Breeding and Genomics Centre, Wageningen University, PO Box 338, 6700 AH, Wageningen, The Netherlands. bert.dibbits@wur.nl.
Back, Willem
  • Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 112-114, 3584 CM, Utrecht, The Netherlands. W.Back@uu.nl.
  • Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, B-9820, Merelbeke, Belgium. W.Back@uu.nl.
Leegwater, Peter A J
  • 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.

MeSH Terms

  • Alleles
  • Animals
  • Breeding
  • Codon, Nonsense / genetics
  • Exons
  • Female
  • Genome-Wide Association Study
  • Horse Diseases / genetics
  • Horses
  • Humans
  • Hydrocephalus / genetics
  • Hydrocephalus / pathology
  • Inbreeding
  • N-Acetylgalactosaminyltransferases / genetics
  • Polymorphism, Single Nucleotide
  • Pregnancy

References

This article includes 40 references
  1. Ducro BJ. Relevance of test information in horse breeding. PhD thesis. 2011.
  2. FAO. Secondary guidelines for development of national farm animal genetic resources management plans: management of small populations at risk. Rome, Italy. 1998.
  3. Falconer DS, Mackay FCT. Introduction to quantitative genetics. Harlow, Essex, England: Longman Group Ltd.; 1996.
  4. van Vliet LMW, Back W. Quantitative analysis of genetic traits related to Friesian horses admitted to a veterinary teaching hospital (1995–2003). Proceedings of the European Veterinary Conference “Voorjaarsdagen” April 2006; Amsterdam, The Netherlands. 2006 p. 68.
  5. Boerma S, Back W, Sloet van Oldruitenborgh-Oosterbaan MM. The Friesian horse breed: a clinical challenge to the equine veterinarian?. Equine Vet Educ 2012;24:66–71.
    doi: 10.1111/j.2042-3292.2011.00302.xgoogle scholar: lookup
  6. Sipma KD, Cornillie P, Saulez MN, Stout TAE, Voorhout G, Back W. Phenotypic characteristics of hydrocephalus in stillborn Friesian foals. Vet Pathol 2013;50:1037–42.
    doi: 10.1177/0300985813488955pubmed: 23676552google scholar: lookup
  7. Ojala M, Ala-Huikku J. Inheritance of hydrocephalus in horses. Equine Vet J 1992;24:140–3.
    doi: 10.1111/j.2042-3306.1992.tb02799.xpubmed: 1582393google scholar: lookup
  8. Ferris RA, Sonnis J, Webb B, Lindholm A, Hassel D. Hydrocephalus in an American Miniature horse foal: a case report and review. J Equine Vet Sci 2011;31:611–4.
    doi: 10.1016/j.jevs.2011.03.005google scholar: lookup
  9. Oey L, Müller JMV, Klopmann TV, Jacobsen B, Beineke A, Feige K. Diagnosis of internal and external hydrocephalus in a warmblood foal using magnetic resonance imaging. Tierarztl Prax 2011;39(G):41–5.
    pubmed: 22138744
  10. Bowman RW. Congenital hydrocephalus in 2 foals. Mod Vet Pract 1980;61:862–4.
    pubmed: 7421786
  11. Rekate HL. The definition and classification of hydrocephalus: a personal recommendation to stimulate debate. Cerebrospinal Fluid Res 2008;5:2.
    doi: 10.1186/1743-8454-5-2pmc: PMC2263019pubmed: 18211712google scholar: lookup
  12. Carbery JT. A case of equine hydrocephalus. N Z Vet J 1979;27:158.
    doi: 10.1080/00480169.1979.34633pubmed: 291822google scholar: lookup
  13. Crowe MW, Swerczek TW. Equine congenital defects. Am J Vet Res 1985;46:353–8.
    pubmed: 3994101
  14. Ekici AB, Hilfinger D, Jatzwauk M, Thiel CT, Wenzel D, Lorenz I. Disturbed Wnt signalling due to a mutation in CCDC88C causes an autosomal recessive non-syndromic hydrocephalus with medial diverticulum. Molec Syndromol 2010;1:99–112.
    pmc: PMC2957845pubmed: 21031079
  15. Drielsma A, Jalas C, Simonis N, Desir J, Simanovsky N, Pirson I. Two novel CCDC88C mutations confirm the role of DAPLE in autosomal recessive congenital hydrocephalus. J Med Genet 2012;49:708–12.
    doi: 10.1136/jmedgenet-2012-101190pubmed: 23042809google scholar: lookup
  16. Al-Dosari MS, Al-Owain M, Tulbah M, Kurdi W, Adly N, Al-Hemidan A. Mutation in MPDZ causes severe congenital hydrocephalus. J Med Genet 2013;50:54–8.
    doi: 10.1136/jmedgenet-2012-101294pubmed: 23240096google scholar: lookup
  17. Rosenthal A, Joulet M, Kenwrick S. Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus. Nature Genet 1992;2:107–12.
    doi: 10.1038/ng1092-107pubmed: 1303258google scholar: lookup
  18. Zhang J, Williams MA, Rigamonti D. Genetics of human hydrocephalus. J Neurol 2006;253:1255–66.
    doi: 10.1007/s00415-006-0245-5pmc: PMC1705504pubmed: 16773266google scholar: lookup
  19. Colleau JJ. An indirect approach to the extensive calculation of relationship coefficients. Genet Sel Evol 2002;34:409–21.
    doi: 10.1186/1297-9686-34-4-409pmc: PMC2705453pubmed: 12270102google scholar: lookup
  20. VanRaden PM. Efficient methods to compute genomic predictions. J Dairy Sci 2008;91:4414–23.
    doi: 10.3168/jds.2007-0980pubmed: 18946147google scholar: lookup
  21. Calus MPL. calc_grm–a programme to compute pedigree, genomic, and combined relationship matrices. Animal Breeding and Genomics Centre, Wageningen UR Livestock Research 2013.
  22. Orr N, Back W, Gu J, Leegwater P, Govindarajan P, Conroy J. Genome-wide SNP association-based localization of a dwarfism gene in Friesian dwarf horses. Anim Genet 2010;41(Suppl 2):2–7.
    doi: 10.1111/j.1365-2052.2010.02091.xpubmed: 21070269google scholar: lookup
  23. Aulchenko YS, Ripke S, Isaacs A, van Duijn CM. GenABEL: an R library for genome-wide association analysis. Bioinformatics 2007;23:1294–6.
    doi: 10.1093/bioinformatics/btm108pubmed: 17384015google scholar: lookup
  24. Mokry M, Feitsma H, Nijman IJ, de Bruijn E, van der Zaag PJ, Guryev V. Accurate SNP and mutation detection by targeted custom microarray-based genomic enrichment of short-fragment sequencing libraries. Nucleic Acids Res 2010;38.
    doi: 10.1093/nar/gkq072pmc: PMC2879533pubmed: 20164091google scholar: lookup
  25. Harakalova M, Mokry M, Hrdlickova B, Renkens I, Duran K, van Roekel H. Multiplexed array-based and insolution genomic enrichment for flexible and cost-effective targeted next-generation sequencing. Nat Protoc 2011;6:1870–86.
    doi: 10.1038/nprot.2011.396pubmed: 22051800google scholar: lookup
  26. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009;25:1754–60.
    doi: 10.1093/bioinformatics/btp324pmc: PMC2705234pubmed: 19451168google scholar: lookup
  27. Hartl DL, Clark AG. Principles of population genetics. Sunderland, Massachusetts, USA: Sinauer Associates Inc. Publishers; 2007.
  28. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263–5.
    doi: 10.1093/bioinformatics/bth457pubmed: 15297300google scholar: lookup
  29. Wade CM, Giulotto E, Sigurdsson S, Zoli M, Gnerre S, Imsland F. Genome sequence, comparative analysis, and population genetics of the domestic horse. Science 2009;326:865–7.
    doi: 10.1126/science.1178158pmc: PMC3785132pubmed: 19892987google scholar: lookup
  30. Stevens E, Carss KJ, Cirak S, Foley AR, Torelli S, Willer T. Mutations in B3GALNT2 cause congenital muscular dystrophy and hypoglycosylation of α-dystroglycan. Am J Hum Genet 2013;92:354–65.
    doi: 10.1016/j.ajhg.2013.01.016pmc: PMC3591840pubmed: 23453667google scholar: lookup
  31. Hedberg C, Oldfors A, Darin N. B3GALNT2 is a gene associated with congenital muscular dystrophy with brain malformations. Eur J Hum Genet 2014;22:707–10.
    doi: 10.1038/ejhg.2013.223pmc: PMC3992579pubmed: 24084573google scholar: lookup
  32. Buck BC, Schenk H, Imbschweiler I, Kuiper H, Wohlsein P, Distl O. A case of a congenital high-grade hydrocephalus internus and Dandy-Walker syndrome in a black and white German Holstein calf. DTW Dtsch Tierarztl Wochenschr 2009;116:220–6.
    pubmed: 19537044
  33. Sharda R, Ingole SP. Congenital bilateral hydrocephalus in a Jersey cow calf- a case report. Indian Vet J 2002;79:965–6.
  34. Keller KA, Guzman DS, Muthuswamy A, Forrest LJ, Steinberg H, Sladky K. Hydrocephalus in a yellow-headed Amazon parrot (Amazona ochrocephala oratrix). J Avian Med Surg 2011;25:216–24.
    doi: 10.1647/2010-005.1pubmed: 22216723google scholar: lookup
  35. Thomas WB. Hydrocephalus in dogs and cats. Vet Clin North Am Small Anim Pract 2010;40:143–59.
    doi: 10.1016/j.cvsm.2009.09.008pubmed: 19942061google scholar: lookup
  36. Davies DAR. Hydrocephalus in sheep. Vet Rec 1998;142:120.
    pubmed: 9501397
  37. Davy BE, Robinson ML. Congenital hydrocephalus in hy3 mice is caused by a frameshift mutation in Hydin, a large novel gene. Hum Mol Genet 2003;12:1163–70.
    doi: 10.1093/hmg/ddg122pubmed: 12719380google scholar: lookup
  38. Durbeej M, Henry MD, Campbell KP. Dystroglycan in development and disease. Curr Opin Cell Biol 1998;10:594–601.
    doi: 10.1016/S0955-0674(98)80034-3pubmed: 9818169google scholar: lookup
  39. Godfrey C, Foley AR, Clement E, Muntoni F. Dystroglycanopathies: coming into focus. Curr Opin Genet Dev 2011;21:278–85.
    doi: 10.1016/j.gde.2011.02.001pubmed: 21397493google scholar: lookup
  40. Godfrey C, Clement E, Mein R, Brockington M, Smith J, Talim B. Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan. Brain 2007;130:2725–35.
    doi: 10.1093/brain/awm212pubmed: 17878207google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.