Journal of Biosocial Science

As this article doesn't contain an abstract, the image below is necessary to enable the article to be indexed by certain search engines. The resolution of the full-text PDF is much higher than that shown here.


M.  LIMA  a1, M.  SMITH  a2, C.  SILVA  a1, A.  ABADE  a3, F.  MAYER  a4 and P.  COUTINHO  a5
a1 Department of Biology, University of the Azores, Portugal
a2 Department of Anthropology, University of Durham, UK
a3 Department of Anthropology, University of Coimbra, Portugal
a4 Department of Biological Sciences, University of Quebec in Montreal, Montreal, Canada
a5 Department of Neurology, Hospital of Porto, Portugal


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 1 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.