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Segmental Duplications Flank the Multiple Sclerosis Locus on Chromosome 17q

    • 1 Department of Human Genetics, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095, USA
    • 2 Department of Pathology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, California 90095, USA
    • 3 Department of Molecular Medicine, National Public Health Institute, 00290 Helsinki, Finland
    • 4 Department of Medical Genetics, University of Helsinki, 00290 Helsinki, Finland
    • 5 Department of Clinical Chemistry, University of Helsinki, 00290 Helsinki, Finland
    • 6 The Finnish Genome Center, University of Helsinki, 00290 Helsinki, Finland
    • 7 Research Program in Molecular Medicine at Biomedicum, 00290 Helsinki, Finland
    • 8 Department of Genetics, Center for Computational Genomics, and the Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106, USA
    • 9 Department of Laboratory Diagnostics, Helsinki University Central Hospital, 00290 Helsinki, Finland
Published July 15, 2004. Vol 14 Issue 8, pp. 1483-1492. https://doi.org/10.1101/gr.2340804
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Abstract

Large chromosomal rearrangements, duplications, and inversions are relatively common in mammalian genomes. Here we report interesting features of DNA strands flanking a Multiple Sclerosis (MS) susceptibility locus on Chromosome 17q24. During the positional cloning process of this 3-Mb locus, several markers showed a radiation hybrid clone retention rate above the average (1.8-fold), suggestive for the existence of duplicated sequences in this region. FISH studies demonstrated multiple signals with three of the tested regional BACs, and 24 BACs out of 187 showed evidence for duplication in shotgun sequence comparisons of the 17q22–q24 region. Specifically, the MS haplotype region proved to be flanked by palindromic sequence stretches and by long segmental intrachromosomal duplications in which highly homologous DNA sequences (>96% identity) are present at both ends of the haplotype. Moreover, the 3-Mb DNA segment, flanked by the duplications, is inverted in the mouse genome when compared with the orientation in human and chimp. The segmental duplication architecture surrounding the MS locus raises the possibility that a nonallelic homologous recombination between duplications could affect the biological activity of the regional genes, perhaps even contributing to the genetic background of MS.

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