TY - JOUR
T1 - A shared haplotype for dentatorubropallidoluysian atrophy (DRPLA) in Italian families testifies of the recent introduction of the mutation
AU - Veneziano, Liana
AU - Mantuano, Elide
AU - Catalli, Claudio
AU - Gellera, Cinzia
AU - Durr, Alexandra
AU - Romano, Silvia
AU - Spadaro, Maria
AU - Frontali, Marina
AU - Novelletto, Andrea
PY - 2014
Y1 - 2014
N2 - To clarify the population history of dentatorubropallidoluysian atrophy (DRPLA) in Italy and to date back the introduction of the mutation, we reconstructed extended haplotypes flanking the CAG repeat in 10 patients of Italian ancestry, analyzing their similarity/dissimilarity as a function of distance from the CAG repeat. Our aim was to compare the hypothesis of a single, recent genealogy connecting all the observed haplotypes with the alternative hypothesis of multiple introductions by more distantly related haplotypes from outer sources. Polymorphic DNA markers were chosen to cover a region of 153 kb flanking the CAG repeat, that is, informative for dating the age of the DNA segment unaffected by recombination. In all patients, an expansion of the ATN1 CAG segment was confirmed residing onto the same narrow haplotype described to be associated with the CAG expansion in the Japanese and Portuguese populations. We also observed the disruption of the DRPLA haplotype at longer distances, on both sides of the CAG. Our results are compatible with a single founder in the last 600 years, most likely before the last 270 years. These estimates for the Sicilian population largely overlap a period in which the Japanese haplotype with the DRPLA mutation could have been introduced by the Portuguese maritime travelers.
AB - To clarify the population history of dentatorubropallidoluysian atrophy (DRPLA) in Italy and to date back the introduction of the mutation, we reconstructed extended haplotypes flanking the CAG repeat in 10 patients of Italian ancestry, analyzing their similarity/dissimilarity as a function of distance from the CAG repeat. Our aim was to compare the hypothesis of a single, recent genealogy connecting all the observed haplotypes with the alternative hypothesis of multiple introductions by more distantly related haplotypes from outer sources. Polymorphic DNA markers were chosen to cover a region of 153 kb flanking the CAG repeat, that is, informative for dating the age of the DNA segment unaffected by recombination. In all patients, an expansion of the ATN1 CAG segment was confirmed residing onto the same narrow haplotype described to be associated with the CAG expansion in the Japanese and Portuguese populations. We also observed the disruption of the DRPLA haplotype at longer distances, on both sides of the CAG. Our results are compatible with a single founder in the last 600 years, most likely before the last 270 years. These estimates for the Sicilian population largely overlap a period in which the Japanese haplotype with the DRPLA mutation could have been introduced by the Portuguese maritime travelers.
KW - ATN1
KW - dentatorubropallidoluysian atrophy
KW - DRPLA
KW - gene flow
KW - genetic dating
KW - haplotype/polyglutamine expansion diseases
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U2 - 10.1038/jhg.2013.137
DO - 10.1038/jhg.2013.137
M3 - Article
C2 - 24401908
AN - SCOPUS:84896926510
VL - 59
SP - 153
EP - 157
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 3
ER -