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Mapping of the bovine spinal muscular atrophy locus to Chromosome 24

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Abstract

A hereditary form of spinal muscular atrophy (SMA) caused by an autosomal recessive gene has been reported for American Brown-Swiss cattle and in advanced backcrosses between American Brown-Swiss and many European brown cattle breeds. Bovine SMA (bovSMA) bears remarkable resemblance to the human SMA (SMA1). Affected homozygous calves also show progressive symmetric weakness and neurogenic atrophy of proximal muscles. The condition is characterized by severe muscle atrophy, quadriparesis, and sternal recumbency as result of neurogenic atrophy. We report on 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). Linkage analysis of a complex pedigree of German Braunvieh cattle revealed a recombination fraction of 0.06 and a three-point lod score of 11.82. The results of linkage and haplotyping analysis enable a marker-assisted selection against bovSMA based on four microsatellite markers most telomeric on BTA24 to a moderate accuracy of 89–94%. So far, this region is not orthologous to any human chromosome segments responsible for twelve distinct disease phenotypes of autosomal neuropathies. Our results indicate the apoptosis-inhibiting protein BCL2 as the most promising positional candidate gene causing bovSMA. Our findings offer an attractive animal model for a better understanding of human forms of SMA and for a probable anti-apoptotic synergy of SMN-BCL2 aggregates in mammals.

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Author notes

  1. Detlef Pietrowski

    Present address: IVF-Ambulanz/Fors-chung, Universitäts-Frauenklinik, Hugstetter Str. 55, D-79106, Freiburg, Germany

Authors and Affiliations

  1. Lehrstuhl für Tierzucht und Allgemeine Landwirtschaftslehre, Ludwig-Maximilians-Universität München, Veterinärstr. 13, D-80539, München, Germany

    Ivica Medugorac, Juliane Kemter, Detlef Pietrowski & Martin Förster

  2. Tierzuchtforschung e.V. München, Senator-Gerauer-Str. 23, D-85586, Grub, Germany

    Ingolf Russ & Martin Förster

  3. Lehr-und Versuchsgut Oberschleißheim, Tierärztlichen Fakultät der Ludwig-Maximilians-Universität München, St. Hubertusstr. 12, D-85764, Oberschleißheim, Germany

    Stefan Nüske

  4. Bayerische Landesanstalt für Landwirtschaft, Institut für Tierzucht, Grub, Prof.-Dürrwaechter-Platz 1, D-85586, Poing, Germany

    Horst-Dieter Reichenbach

  5. Lehrstuhl für Allgemeine Pathologie und Neuropathologie, Ludwig-Maximilians-Universität München, Veterinärstr. 13, D-80539, München, Germany

    Wolfgang Schmahl

Authors
  1. Ivica Medugorac
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  2. Juliane Kemter
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Correspondence to Ivica Medugorac.

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Medugorac, I., Kemter, J., Russ, I. et al. Mapping of the bovine spinal muscular atrophy locus to Chromosome 24. Mammalian Genome 14, 383–391 (2003). https://doi.org/10.1007/s00335-002-3024-3

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  • DOI: https://doi.org/10.1007/s00335-002-3024-3

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