Studies On Genetic Linkage, (CAG) N Array And The Mechanism Of (CAG)n Expansion Instability Of MJD1 Gene In Chinese Machado-Joseph Disease

Machado-Joseph disease(MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron, oculomotor systems,and distal muscular atrophy. Although it was first reported in familes of Portuguese-Azorean descent,MJD has also been described in non- Azorean families from various countries, being one of the most common hereditary spino- cerebellar degenerations.In order to confirm the MJD reported in Chinese families and to attempt to narrow the candidate region of this gene, We did a linkage study of 4 multigenerational MJD Chinese pedigrees with 13 microsatellite DNA on 14q in the first section. Pairwise linkage analysis indicate the maximal lod score between MJD and D14S81 is 4. 91 at θ = 0. 00. Meanwhile, lod scores exceeding 3.0 were also observed for AFM343vf1 and D14S48.Multipoint linkage analysis resulted in an even higher likelihood of linkage at D14S280 (Zmax= 8. 3724, 9 = 0. 00) . The haplotype segregation analysis found that all affected subjects in each family conserved the same haplotype. In...