Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington's disease.
We studied the allelic profile of CAG and CCG repeats in 61 Brazilian individuals in 21 independent families affected by Huntington's disease (HD). Thirteen individuals had two normal alleles for HD, two had one mutable normal allele and no HD phenotype, and forty-six patients carried at least one expanded CAG repeat allele. Forty-five of these individuals had one expanded allele and one individual had one mutable normal allele (27 CAG repeats) and one expanded allele (48 CAG repeats). Eleven of these forty-five subjects had a mutant allele with reduced penetrance, and thirty-four patients had a mutant allele with complete penetrance. Inter- and intragenerational investigations of CAG repeats were also performed. We found a negative correlation between the number of CAG repeats and the age of disease onset (r=-0.84; P<0.001) and no correlation between the number of CCG repeats and the age of disease onset (r=0.06). We found 40 different haplotypes and the analysis showed that (CCG)(10) was linked to a CAG normal allele in 19 haplotypes and to expanded alleles in two haplotypes. We found that (CCG)(7) was linked to expanded CAG repeats in 40 haplotypes (95.24%) and (CCG)(10) was linked to expanded CAG repeats in only two haplotypes (4.76%). Therefore, (CCG)(7) was the most common allele in HD chromosomes in this Brazilian sample. It was also observed that there was a significant association of (CCG)(7) with the expanded CAG alleles (χ(2)=6.97, P=0.0084). Worldwide, the most common CCG alleles have 7 or 10 repeats. In Western Europe, (CCG)(7) is the most frequent allele, similarly to our findings.
Programa de Pós-Graduação em Neurologia, UNIRIO, Rio de Janeiro, Brazil.
Luciana de A
Lde A
Agostinho
Catielly F
CF
Rocha
Enrique
E
Medina-Acosta
Hazel N
HN
Barboza
Antônio F Alves
AF
da Silva
Simão P F
SP
Pereira
Iane Dos Santos
Idos S
da Silva
Eduardo R
ER
Paradela
André L dos S
AL
Figueiredo
Eduardo de M
Ede M
Nogueira
Regina M P
RM
Alvarenga
Pedro
P
Hernan Cabello
Suely R
SR
dos Santos
Carmen L A
CL
Paiva
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D001938:Brazil; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics*; D018911:Trinucleotide Repeats / Q000235:genetics*
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins