Mutational origin of Machado-Joseph disease in the Australian Aboriginal communities of Groote Eylandt and Yirrkala.

Sandra Martins, Bing-Wen Soong, Virginia C. N. Wong, Paola Giunti, Giovanni Stevanin, Laura P. W. Ranum, Hidenao Sasaki, Olaf Riess, Shoji Tsuji, Paula Coutinho, António Amorim, Jorge Sequeiros, Garth A. Nicholson
Arch Neurol. 2012-06-01; 69(6):
DOI: 10.1001/archneurol.2011.2504

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1. Arch Neurol. 2012 Jun;69(6):746-51. doi: 10.1001/archneurol.2011.2504.

Mutational origin of Machado-Joseph disease in the Australian Aboriginal
communities of Groote Eylandt and Yirrkala.

Martins S(1), Soong BW, Wong VC, Giunti P, Stevanin G, Ranum LP, Sasaki H, Riess
O, Tsuji S, Coutinho P, Amorim A, Sequeiros J, Nicholson GA.

Author information:
(1)Institute of Molecular Pathology and Immunology, University of Porto, Porto,

OBJECTIVE: To determine whether the presence of Machado-Joseph disease (MJD, also
spinocerebellar ataxia type 3 [SCA3]) among Australian aborigines was caused by a
new mutational event or by the introduction of expanded alleles from other
DESIGN: We sequenced a region of 4 kilobases (kb), encompassing the CAG repeat
within the ATXN3 gene, in 2 affected Australian aboriginal families and compared
them with the Joseph and Machado lineages described before. Full-extended
haplotypes (including also more distant single-nucleotide polymorphisms and
flanking short tandem repeats) were assessed by segregation and allele-specific
amplification. A phylogenetic tree was inferred from genetic distances, and age
of the Australasian Joseph-derived lineage was estimated.
SETTING: The aboriginal communities of Groote Eylandt and Yirrkala, in the
Northern Territories, Australia (local ethics institutional permission was
granted, and both community and individual informed consent was obtained).
SUBJECTS: A convenience sample of 19 patients and unaffected relatives, from 2
Australian aboriginal families affected with MJD; 40 families with MJD of
multiethnic origins and 50 unrelated Asian control subjects.
RESULTS: The 2 aboriginal families shared the same full haplotype, including 20
single-nucleotide polymorphisms:TTGATCGAGC-(CAG)(Exp)-CACCCAGCGC, that is, the
Joseph lineage with a G variant in rs56268847.Among 33 families with the Joseph
lineage, this derived haplotype was found only in 5 of 16 Taiwanese, all 3
Indian,and 1 of 3 Japanese families analyzed.
CONCLUSION: A related-extended MJD haplotype shared by Australian aborigines and
some Asian families (a Joseph-derived lineage) suggests a common ancestor for
all, dating back more than 7000 years.

DOI: 10.1001/archneurol.2011.2504
PMID: 22351852 [Indexed for MEDLINE]

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