Linked polymorphic DNA markers in the prediction of X-linked muscular dystrophy

Authors

  • M. LINDLÖF,

    1. *Department of Medical Genetics, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland
    2. †Folkhälsan Institute of Genetics, P.O. box 819, SF-00290 Helsinki, Finland
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  • P. SISTONEN,

    1. ‡Finnish Red Cross, Blood Transfusion Service, Kivihaantie 7, SF-00310 Helsinki, Finland
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  • A. de la CHAPELLE

    1. *Department of Medical Genetics, University of Helsinki, Haartmaninkatu 3, SF-00290 Helsinki, Finland
    2. †Folkhälsan Institute of Genetics, P.O. box 819, SF-00290 Helsinki, Finland
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Summary

Ten polymorphic DNA markers, including gene specific markers of loci DXS164 and DXS206, were tested for allele frequencies, degree of heterozygosity and linkage in 34 Finnish families with X-linked muscular dystrophy. With the exception of the BamHI RFLP of DXS164 subclone pERT87-15, allele frequencies and the degree of heterozygosity failed to show any significant deviation from the data published elsewhere. We document a high degree of linkage disequilibrium between several RFLPs belonging to locus DXS164. Our linkage data include one recombination between DMD and DXS164 enabling a tentative location of the mutation site distal to DXS164. The maximum lod score for linkage between the disease locus and DX164 was 7.828 at a recombination fraction of 0.02. According to our data DXS28 and DXS43 may be located further away from the disease locus than previously thought. We use only gene specific markers for genetic counselling. Excluding deletions, 97.1 % of women were heterozygous for at least one such marker. A diagnostic procedure in which useful information can be obtained in over 90 % of all diagnostic situations, using only four filters, is proposed.

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