Abstract
Nearly 30 hereditary disorders in humans result from an increase in the number of copies of simple repeats in genomic DNA. These DNA repeats seem to be predisposed to such expansion because they have unusual structural features, which disrupt the cellular replication, repair and recombination machineries. The presence of expanded DNA repeats alters gene expression in human cells, leading to disease. Surprisingly, many of these debilitating diseases are caused by repeat expansions in the non-coding regions of their resident genes. It is becoming clear that the peculiar structures of repeat-containing transcripts are at the heart of the pathogenesis of these diseases.
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Acknowledgements
I thank W. Krzyzosiak, R. Lahue, K. Lobachev, C. McMurray, D. Monckton, C. Pearson, M. Swanson, K. Usdin and R. Wells for sharing their ideas and unpublished results. I also extend my gratitude to all the participants of the 5th International Conference on Unstable Microsatellites and Human Disease (Granada, Spain, 2006) for their intense and productive discussions, which helped to shape this review. I am indebted to my wife, Kate, for her invaluable critical comments. I thank J. White and P. White for their generous support. This work was supported by the National Institutes of Health.
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Mirkin, S. Expandable DNA repeats and human disease. Nature 447, 932–940 (2007). https://doi.org/10.1038/nature05977
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DOI: https://doi.org/10.1038/nature05977
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