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The mouse homolog of FRG1, a candidate gene for FSHD, maps proximal to the myodystrophy mutation on chromosome 8

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Abstract

The human autosomal dominant neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD) is associated with deletions within a complex tandem DNA repeat (D4Z4) on Chromosome (Chr) 4q35. The molecular mechanism underlying this association of FSHD with DNA rearrangements is unknown, and, thus far, no gene has been identified within the repeat. We isolated a gene mapping 100 kb proximal to D4Z4 (\(\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{F} \)SHD \(\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{R} \)egion \(\underset{\raise0.3em\hbox{$\smash{\scriptscriptstyle-}$}}{G} \)ene 1:FRG1), but were unable to detect any alterations in total or allele-specific mRNA levels of FRG1 in FSHD patients. Human Chr 4q35 exhibits synteny homology with the region of mouse Chr 8 containing the gene for the myodystrophy mutation (myd), a possible mouse homolog of FSHD. We report the cloning of the mouse gene (Frg1) and show that it maps to mouse Chr 8. Using a cross segregating the myd mutation and the European Collaborative Interspecific Backcross, we showed that Frg1 maps proximal to the myd locus and to the Clc3 and Ant1 genes.

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Authors and Affiliations

  1. School of Biological Sciences, The University of Manchester, 3.239 Stopford Building, Oxford Road, M13 9PT, Manchester, UK

    Prabhjit K. Grewal & Jane E. Hewitt

  2. MGC-Department of Human Genetics, Sylvius Laboratory, Leiden University Leiden, The Netherlands

    Judith C. T. van Deutekom, Richard J. L. F. Lemmers & Rune R. Frants

  3. Department of Pediatrics, University of Iowa, Iowa City, Iowa USA

    Kate A. Mills & Kathy D. Mathews

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  1. Prabhjit K. Grewal
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  2. Judith C. T. van Deutekom
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  3. Kate A. Mills
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  4. Richard J. L. F. Lemmers
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  5. Kathy D. Mathews
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  6. Rune R. Frants
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  7. Jane E. Hewitt
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Grewal, P.K., van Deutekom, J.C.T., Mills, K.A. et al. The mouse homolog of FRG1, a candidate gene for FSHD, maps proximal to the myodystrophy mutation on chromosome 8. Mammalian Genome 8, 394–398 (1997). https://doi.org/10.1007/s003359900454

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  • DOI: https://doi.org/10.1007/s003359900454

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