Mutational Origin of Machado-Joseph Disease in the Australian Aboriginal Communities of Groote Eylandt and Yirrkala

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Sandra Martins (Author) Other; Bing Wen Soong (Author) Other; Virginia C N Wong (Author) Other; Paola Giunti (Author) Other; Giovanni Stevanin (Author) Other; Laura P W Ranum (Author) Other; Hidenao Sasaki (Author) Other; Olaf Riess (Author) Other; Shoji Tsuji (Author) Other; Paula Coutinho (Author) Other; Antonio Amorim (Author) FCUP; Jorge Sequeiros (Author) ICBAS; Garth A Nicholson (Author) Other

Journal

Title: Archives of Neurology

Vol. 69

Pages: 746-751

ISSN: 0003-9942

Publisher: American Medical Association

Indexing

ISI Web of Knowledge - 18 Citations

Scopus - 21 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-002-9DC

DOI: 10.1001/archneurol.2011.2504

Abstract (EN): 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. Arch Neurol. 2012; 69(6): 746-751. Published online February 20, 2012. doi:10.1001/archneurol.2011.2504

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6