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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.

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  • 1Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal.

Abstract

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 populations.

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.

PMID:
22351852
DOI:
10.1001/archneurol.2011.2504
[PubMed - indexed for MEDLINE]
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