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. 2001 Feb;68(2):523-8.
doi: 10.1086/318184. Epub 2000 Dec 20.

Ancestral origins of the Machado-Joseph disease mutation: a worldwide haplotype study

C Gaspar  1 , I Lopes-Cendes, S Hayes, J Goto, K Arvidsson, A Dias, I Silveira, P Maciel, P Coutinho, M Lima, Y X Zhou, B W Soong, M Watanabe, P Giunti, G Stevanin, O Riess, H Sasaki, M Hsieh, G A Nicholson, E Brunt, J J Higgins, M Lauritzen, L Tranebjaerg, V Volpini, N Wood, L Ranum, S Tsuji, A Brice, J Sequeiros, G A Rouleau
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Ancestral origins of the Machado-Joseph disease mutation: a worldwide haplotype study

C Gaspar et al. Am J Hum Genet. 2001 Feb.

Abstract

Machado-Joseph disease (MJD) is an autosomal dominant neurodegenerative disorder originally described in families of Portuguese-Azorean ancestry. The cloning of the MJD1 gene allowed identification of the disease in many other populations, and MJD is now known to be the most common cause of dominant spinocerebellar ataxia. The hypothesis that its present world distribution could result from the spread of an original founder mutation has been raised, both at historical and molecular levels. In the present study, we tested this hypothesis by linkage-disequilibrium analysis of tightly linked polymorphisms and by haplotype comparison, in 249 families from different countries. We typed five microsatellite markers surrounding the MJD1 locus (D14S1015, D14S995, D14S973, D14S1016, and D14S977), and three intragenic single-base-pair polymorphisms (A(669)TG/G(669)TG, C(987)GG/G(987)GG, and TAA(1118)/TAC(1118)). The results show two different haplotypes, specific to the island of origin, in families of Azorean extraction. In families from mainland Portugal, both Azorean haplotypes can be found. The majority of the non-Portuguese families also share the same intragenic haplotype seen in the families coming from the island of Flores, but at least three other haplotypes were seen. These findings suggest two introductions of the mutation into the Portuguese population. Worldwide, the sharing of one intragenic haplotype by the majority of the families studied implies a founder mutation in MJD.

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Figures

Figure 1
Figure 1
Overall intragenic haplotype frequencies. Frequency of the eight possible haplotypes formed by the three intragenic polymorphisms. All eight combinations were present in the control population; in contrast, only four of the possible haplotypes were seen in the MJD families, with haplotype A-C-A being present in >70% of the total MJD families used in this study.
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References

Electronic-Database Information

    1. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim (for Machado-Joseph disease [MIM 109150])

References

    1. Coutinho P, Andrade C (1978) Autosomal dominant system degeneration in Portuguese families of the Azores Islands: a new genetic disorder involving cerebellar, pyramidal, extrapyramidal and spinal cord motor functions. Neurology 28:703–709 - PubMed
    1. Coutinho P, Calheiros JM, Andrade C (1977) Sobre uma nova doenca degenerativa do sistema nervoso central transmitida de modo autossomico dominante e aspectos familiares originarios dos Acores. O Médico 82:1–3
    1. Devlin B, Risch N (1995) A comparison of linkage disequilibrium measures for fine-scale mapping. Genomics 29:311–322 - PubMed
    1. Gaspar C, Lopes-Cendes I, DeStefano AL, Maciel P, Silveira I, Coutinho P, MacLeod P, Sequeiros J, Farrer LA, Rouleau GA (1996) Linkage disequilibrium analysis in Machado-Joseph disease patients of different ethnic origins. Hum Genet 98:620–624 - PubMed
    1. Goto J, Watanabe M, Ichikawa Y, Yee SB, Ihara N, Endo K, Igarashi S, Takiyama Y, Gaspar C, Maciel P, Tsuji S, Rouleau GA, Kanazawa I (1997) Machado-Joseph disease gene products carrying different carboxyl termini. Neurosci Res 28:373–377 - PubMed

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