OMIA 000939-9913 : Spinal muscular atrophy in Bos taurus

In other species: dog , domestic cat

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 253300 , 253550 , 253400 , 271150

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal Recessive

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2007

Species-specific name: Haplotype BHM

Species-specific symbol: BHM

Mapping: Medugorac et al. (2003) reported "the localization of the gene causing bovSMA within a genomic interval between the microsatellite marker URB031 and the telomeric end of bovine Chromosome (Chr) 24 (BTA24)"

Krebs et al. (2006) refined the mapping "to an interval of approximately 0.8 cM at the very distal end of BTA24". Krebs et al. (2007) narrowed the location to a region containing three comparative positional candidate genes.

In the course of their large-scale study of BovineSNP50 BeadChip haplotypes that are common but never homozygous, VanRaden et al. (2011) confirmed the mapping of this disorder to BTA24 at 58-63Mb (UMD 3.0 genome assembly).

Molecular basis: By examining three comparative positional candidate genes from their mapping results (see Mapping section), Krebs et al. (2007) reported strong evidence that this disorder in cattle is due to a mutation in "FVT1, encoding 3-ketodihydrosphingosine reductase, which catalyzes a crucial step in the glycosphingolipid metabolism". Specifically, the mutation is "a G-to-A missense mutation that changes Ala-175 to Thr". Interestingly, the FVT1 gene, officially known as KDSR, is not included in the list of genes in which mutations result in SMA in humans.

In their table of reduced-fertility haplotypes, Cole et al. (2014) list this KDSR mutation as being the causal mutation for haplotype BHM, which is located at 62,118,139– 62,156,760bp on chromosome BTA24.

Cagnotti et al. (2020) reported that this same disorder in an Italian family of the Blonde d'Aquitaine breed is not due to any mutation in FVT1/KDSR.

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
KDSR 3-ketodihydrosphingosine reductase Bos taurus 24 NC_037351.1 (61638744..61596078) KDSR Homologene, Ensembl, NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Breed(s) Variant Phenotype Gene Allele Type of Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
Braunvieh Spinal muscular atrophy KDSR missense UMD3.1 24 g.62138763G>A c.562G>A p.A188T 2007 17420465 Variant coordinates obtained from or confirmed by EBI's Some Effect Predictor (VEP) tool


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
2020 Cagnotti, G., Cantile, C., Chessa, S., Sacchi, P., D'Angelo, A., Bellino, C. :
Spinal Muscular Atrophy in Blonde D'Aquitaine Calves Is Not Associated With FVT1 Gene Mutation. Front Vet Sci 7:348, 2020. Pubmed reference: 32714947. DOI: 10.3389/fvets.2020.00348.
2019 Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A., Zepeda-Batista, J.L., Parra-Bracamonte, G.M., Núñez-Domínguez, R., Ramírez-Valverde, R., Ruíz-Flores, A. :
Screening genetic diseases prevalence in Braunvieh cattle. Trop Anim Health Prod 51:25-31, 2019. Pubmed reference: 30014197. DOI: 10.1007/s11250-018-1655-y.
2016 Cole, J.B., Null, D.J., VanRaden, P.M. :
Phenotypic and genetic effects of recessive haplotypes on yield, longevity, and fertility. J Dairy Sci 99:7274-88, 2016. Pubmed reference: 27394947. DOI: 10.3168/jds.2015-10777.
2014 Cole, J.B. , VanRaden, P.M., Null, D.J., Hutchison, J.L., Cooper, T.A., Hubbard, S.M. :
Haplotype tests for recessive disorders that affect fertility and other traits. AIP RESEARCH REPORT GENOMIC3 (09-13); :, 2014.
2011 VanRaden, P.M., Olson, K.M., Null, D.J., Hutchison, J.L. :
Harmful recessive effects on fertility detected by absence of homozygous haplotypes. J Dairy Sci 94:6153-61, 2011. Pubmed reference: 22118103. DOI: 10.3168/jds.2011-4624.
2009 Manatrinon, S., Egger-Danner, C., Baumung, R. :
Estimating lethal allele frequencies in complex pedigrees via gene dropping approach using the example of Brown Swiss cattle Archiv fur Tierzucht 52:230-242, 2009.
2008 Parkinson, NJ., Baumer, D., Rose-Morris, A., Talbot, K. :
Candidate screening of the bovine and feline spinal muscular atrophy genes reveals no evidence for involvement in human motor neuron disorders. Neuromuscular Disorders 18:394-7, 2008. Pubmed reference: 18395445. DOI: 10.1016/j.nmd.2008.03.003.
2007 Krebs, S., Medugorac, I., Röther, S., Strässer, K., Förster, M. :
A missense mutation in the 3-ketodihydrosphingosine reductase FVT1 as candidate causal mutation for bovine spinal muscular atrophy. Proc Natl Acad Sci U S A 104:6746-51, 2007. Pubmed reference: 17420465. DOI: 10.1073/pnas.0607721104.
2006 Krebs, S., Medugorac, I., Russ, I., Ossent, P., Bleul, U., Schmahl, W., Forster, M. :
Fine-mapping and candidate gene analysis of bovine spinal muscular atrophy. Mamm Genome 17:67-76, 2006. Pubmed reference: 16416092. DOI: 10.1007/s00335-005-0102-3.
2005 Joerg, H., Muntwyler, J., Glowatzki-Mullis, ML., Ahrens, E., Asai-Coakwell, M., Stranzinger, G. :
Bovine spinal muscular atrophy: AFG3L2 is not a positional candidate gene. J Anim Breed Genet 122 Suppl 1:103-7, 2005. Pubmed reference: 16130464.
2003 Longeri, M., Perrone, T., Bongioni, G., Bona, M., Zanotti, M., Galli, A. :
Survival motor neuron (SMN) polymorphism in relation to congenital arthrogryposis in two Piedmont calves (piemontese) Genetics Selection Evolution 35:S167-75, 2003.
Medugorac, I., Kemter, J., Russ, I., Pietrowski, D., Nüske, S., Reichenbach, H.D., Schmahl, W., Förster, M. :
Mapping of the bovine spinal muscular atrophy locus to Chromosome 24. Mamm Genome 14:383-91, 2003. Pubmed reference: 12879360. DOI: 10.1007/s00335-002-3024-3.
Siso, S., Pumarola, M., Ferrer, I. :
Cell death and decreased synaptic protein expression in the ventral horn of Holstein-Friesian calves with spinal muscular atrophy Journal of Comparative Pathology 128:132-9, 2003. Pubmed reference: 12634090.
1999 Jull, B.A., Patton, C.S., Haffner, J. :
Lower motor neuronopathy in a Dutch Belted-Sembra bull Journal of Veterinary Diagnostic Investigation 11:177-179, 1999. Pubmed reference: 10098692.
Winter, P., Bago, Z., Podstatzky, L., Speckbacher, G. :
Spinal muscular atrophy in a Brown-Swiss calf - a case report [German] Wiener Tierarztliche Monatsschrift 86:83-87, 1999.
1994 Agerholm, J.S., Basse, A. :
Spinal Muscular Atrophy in Calves of the Red Danish Dairy Breed Veterinary Record 134:232-235, 1994. Pubmed reference: 8197680.
Lidauer, M., Essl, A. :
Estimation of the Frequencies for Recessive Lethal Genes for Spinal Muscular Atrophy, Arachnomelia and Weaver in the Austrian Braunvieh Population Zuchtungskunde 66:54-65, 1994.
1993 Agerholm, J.S., Basse, A., Christensen, K. :
Investigations on the occurrence of hereditary diseases in the Danish cattle population 1989-1991 Acta Veterinaria Scandinavica 34:245-253, 1993. Pubmed reference: 8310897.
Hiraga, T., Leipold, H.W., Cash, W.C., Troyer, D.L. :
Reduced Numbers and Intense Anti-Ubiquitin Immunostaining of Bovine Motor Neurons Affected with Spinal Muscular Atrophy Journal of the Neurological Sciences 118:43-47, 1993. Pubmed reference: 7693876.
Hiraga, T., Leipold, H.W., Vestweber, J.G.E., Cash, W.C., Troyer, D.L. :
Cytoskeletal Proteins in Affected Motor Neurons in Bovine Spinal Muscular Atrophy Progress in Veterinary Neurology 4:137-142, 1993.
Troyer, D., Cash, W.C., Vestweber, J., Hiraga, T., Leipold, H.W. :
Review of Spinal Muscular Atrophy (SMA) in Brown Swiss Cattle Journal of Veterinary Diagnostic Investigation 5:303-306, 1993. Pubmed reference: 8507715.
1992 Dirksen, G., Doll, K., Hafner, A., Hermanns, W., Dahme, E. :
Spinal Muscular Atrophy (SMA) in Calves of Brown Swiss X Deutsches Braunvieh Deutsche Tierarztliche Wochenschrift 99:165-175, 1992. Pubmed reference: 1638959.
Stocker, H., Ossent, P., Heckmann, R., Oertle, C. :
Spinal Muscular Atrophy in Brown Swiss Calves Schweizer Archiv Fur Tierheilkunde 134:97-104, 1992. Pubmed reference: 1566027.
Troyer, D., Leipold, H.W., Cash, W., Vestweber, J. :
Upper Motor Neurone and Descending Tract Pathology in Bovine Spinal Muscular Atrophy Journal of Comparative Pathology 107:305-317, 1992. Pubmed reference: 1469126.
1990 Nielsen, J.S., Andresen, E., Basse, A., Christensen, L.G., Lykke, T., Nielsen, U.S. :
Inheritance of Bovine Spinal Muscular Atrophy Acta Veterinaria Scandinavica 31:253-255, 1990. Pubmed reference: 2260520.
1989 Elhamidi, M., Leipold, H.W., Vestweber, J.G.E., Saperstein, G. :
Spinal Muscular Atrophy in Brown Swiss Calves Journal of Veterinary Medicine Series A-Animal Physiology Pathology and Clinical Veterinary Medicine-Zentralblatt Fur Veterinarmedizin Reihe a 36:731-738, 1989.
1988 Hansen, KM., Krogh, HV., Møller, JE., Elleby, F. :
The recumbent calf syndrome in the Red Danish Milkbreed - A new hereditary disease (in Danish) Dansk VetTidskr. 71:128-132, 1988.

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  • Created by Frank Nicholas on 08 Sep 2008
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