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TitleThe CAG repeat at the Huntington disease gene in the Portuguese population : insights into its dynamics and to the origin of the mutation
Author(s)Costa, Maria do Carmo
Magalhães, Paula
Guimarães, Laura
Maciel, P.
Sequeiros, Jorge
Sousa, Alda
KeywordsTriplet repeat disorders
CAG repeat
HD founder haplotypes
CAG repeat evolution
Issue date2006
PublisherSpringer Verlag
JournalJournal of Human Genetics
Citation"Journal of Human Genetics". ISSN 1434-5161. 51:3 (2006) 189-195.
Abstract(s)Huntington disease (HD) is caused by an expansion of a CAG repeat. This repeat is a dynamic mutation that tends to undergo intergenerational instability. We report the analysis of the CAG repeat in a large population sample (2,000 chromosomes) covering all regions of Portugal, and a haplotype study of (CAG)n and (CCG)n repeats in 140 HD Portuguese families. Intermediate class 2 alleles represented 3.0% of the population; and two expanded alleles (36 and 40 repeats, 0.11%) were found. There was no evidence for geographical clustering of the intermediate or expanded alleles. The Portuguese families showed three different HD founder haplotypes associated with 7-, 9- or 10-CCG repeats, suggesting the possibility of different origins for theHDmutation among this population. The haplotype carrying the 7-CCG repeat was the most frequent, both in normal and in expanded alleles. In general, we propose that three mechanisms, occurring at different times,may lead to the evolution from normal CAGs to full expansion: first, a mutation bias towards larger alleles; then, a stepwise process that could explain the CAGdistributions observed in themore recent haplotypes; and, finally, a pool of intermediate (class 2) alleles more prone to give rise to expanded HD alleles.
Publisher version“The original publication is available at"
AccessOpen access
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee

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