Trinucleotide repeat length instability and age of onset in Huntington's disease

M. Duyao, C. Ambrose, R. Myers, A. Novelletto, F. Persichetti, M. Frontali, S. Folstein, C. Ross, M. Franz, M. Abbott, J. Gray, P. Conneally, A. Young, J. Penney, Z. Hollingsworth, I. Shoulson, A. Lazzarini, A. Falek, M. MacDonald

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Abstract

The initial observation of an expanded and unstable trinucleotide repeat in the Huntington's disease gene has now been confirmed and extended in 150 independent Huntington's disease families. HD chromosomes contained 37-86 repeat units, whereas normal chromosomes displayed 11-34 repeats. The HD repeat length was inversely correlated with the age of onset of the disorder. The HD repeat was unstable in more than 80% of meiotic transmissions showing both increases and decreases in size with the largest increases occurring in paternal transmissions. The targeting of spermatogenesis as a particular source of repeat instability is reflected in the repeat distribution of HD sperm DNA. The analysis of the length and instability of individual repeats in members of these families has profound implications for presymptomatic diagnosis.

Original languageEnglish
Pages (from-to)387-392
Number of pages6
JournalNature Genetics
Volume4
Issue number4
DOIs
StatePublished - Aug 13 1993

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Trinucleotide Repeats
Huntington Disease
Age of Onset
Trinucleotide Repeat Expansion
Chromosomes, Human, Pair 11
Spermatogenesis
Spermatozoa
Chromosomes
Observation
DNA
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Duyao, M., Ambrose, C., Myers, R., Novelletto, A., Persichetti, F., Frontali, M., ... MacDonald, M. (1993). Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genetics, 4(4), 387-392. https://doi.org/10.1038/ng0893-387

Trinucleotide repeat length instability and age of onset in Huntington's disease. / Duyao, M.; Ambrose, C.; Myers, R.; Novelletto, A.; Persichetti, F.; Frontali, M.; Folstein, S.; Ross, C.; Franz, M.; Abbott, M.; Gray, J.; Conneally, P.; Young, A.; Penney, J.; Hollingsworth, Z.; Shoulson, I.; Lazzarini, A.; Falek, A.; MacDonald, M.

In: Nature Genetics, Vol. 4, No. 4, 13.08.1993, p. 387-392.

Research output: Contribution to journalArticle

Duyao, M, Ambrose, C, Myers, R, Novelletto, A, Persichetti, F, Frontali, M, Folstein, S, Ross, C, Franz, M, Abbott, M, Gray, J, Conneally, P, Young, A, Penney, J, Hollingsworth, Z, Shoulson, I, Lazzarini, A, Falek, A & MacDonald, M 1993, 'Trinucleotide repeat length instability and age of onset in Huntington's disease', Nature Genetics, vol. 4, no. 4, pp. 387-392. https://doi.org/10.1038/ng0893-387
Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M et al. Trinucleotide repeat length instability and age of onset in Huntington's disease. Nature Genetics. 1993 Aug 13;4(4):387-392. https://doi.org/10.1038/ng0893-387
Duyao, M. ; Ambrose, C. ; Myers, R. ; Novelletto, A. ; Persichetti, F. ; Frontali, M. ; Folstein, S. ; Ross, C. ; Franz, M. ; Abbott, M. ; Gray, J. ; Conneally, P. ; Young, A. ; Penney, J. ; Hollingsworth, Z. ; Shoulson, I. ; Lazzarini, A. ; Falek, A. ; MacDonald, M. / Trinucleotide repeat length instability and age of onset in Huntington's disease. In: Nature Genetics. 1993 ; Vol. 4, No. 4. pp. 387-392.
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