Segregation distortion of wild-type alleles at the Machado-Joseph disease locus: a study in normal families from the Azores islands (Portugal)

• Autor(a) principal: Bettencourt, Conceição
• Data de Publicação: 2008
• Outros Autores: Fialho, Raquel Nunes, Santos, Cristina, Montiel, Rafael, Bruges-Armas, Jácome, Maciel, P., Lima, Manuela
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/1822/61455
• topic: Azores; Chromosome Segregation; Chromosomes, Human, Pair 14; Humans; Machado-Joseph Disease; Trinucleotide Repeat Expansion; Alleles; SCA3; CAG repeats; Segregation ratio distortion; Wild-type alleles; MJD; Science & Technology

Machado-Joseph disease (MJD) is caused by an expansion of a triplet repeat with a CAG motif at the ATXN3 gene. The putative segregation ratio distortion (SRD) of alleles can play an important role in the non-Mendelian behaviour of triplet repeat loci. To study the stability and infer the segregation patterns of wild-type MJD alleles, the size of the (CAG)(n) tract was analysed in 102 normal sibships, representing 428 meioses. No mutational events were detected during the transmission of alleles. Segregation analysis showed that the smaller alleles were preferentially transmitted (56.9%). Considering maternal meioses alone, such preference was still detected (55.7%) but without statistical significance. A positive correlation was observed for the difference in length between the two alleles constituting the transmitters' genotype (D) and the frequency of transmission of the smaller alleles. The results suggest that small D values are not enough to modify the probability of allele transmission. When transmissions involving genotypes with D <or= 2 were excluded, SRD in favour of the smaller allele became significant for both maternal and paternal transmissions. Therefore, the genotypic composition of the transmitters in a sample to be analysed should influence the ability to detect SRD, acting as a confounding factor.