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Natural selection at the MJD locus : phenotypic diversity, survival and fertility among Machado-Joseph disease patients from the Azores.

Lima, M. and Smith, M. T. and Silva, C. and Abade, A. and Mayer, F. M. and Coutinho, P. (2001) 'Natural selection at the MJD locus : phenotypic diversity, survival and fertility among Machado-Joseph disease patients from the Azores.', Journal of biosocial science., 33 (3). pp. 361-373.


Machado-Joseph Disease (MJD) is an autosomal dominant neurodegenerative disorder of adult onset, associated with the expansion of a (CAG)n tract in the coding region of the causative gene, localized on 14q32.1. Machado-Joseph Disease shows non-Mendelian features typical of other triplet repeat disorders, including clinical heterogeneity, variable age at onset and anticipation. Three phenotypes have been proposed (clinical types 1, 2 and 3). Type 1 is associated with early age at onset and a high repeat number of the CAG sequence, and Types 2 and 3 have later onset and lower numbers of CAG repeats, This paper investigates whether there is selection against the MJD gene, acting through differential survival, nuptiality and fertility associated with clinical type and age at onset. The study sample comprised 40 MJD patients from the Azores (Portugal) having fully documented reproductive histories and known dates of death. The proportion of married patients of each clinical type increased from 0.22 among Type 1 patients, to 0.40 in Type 2 and 0.95 in Type 3, Age at onset and length of survival were also associated with marital status, with the married cases having later mean age at onset and longer mean survival time. In the whole sample, clinical type was associated with fertility, with significantly fewer children born to Type i patients. Among married patients clinical type was not associated with age at marriage, reproductive span or number of children. No reduction of fertility was detected among married patients in whom the onset of MJD was below the age of 50, The authors' interpretation of these results is that the high-repeat CAG haplotypes associated with early age at onset and clinical Type 1 are selected against through reduced survival and fertility. The Fertility component of selection is mediated by nuptiality rather than marital fertility.

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Publisher statement:© 2001 Cambridge University Press
Record Created:22 May 2008
Last Modified:09 Sep 2011 09:23

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