MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events

Stefan Aretz, Rossella Tricarico, Laura Papi, Isabel Spier, Elisa Pin, Sukanya Horpaopan, Emanuela Lucci Cordisco, Monica Pedroni, Dietlinde Stienen, Annamaria Gentile, Anna Panza, Ada Piepoli, Maurizio Ponz De Leon, Waltraut Friedl, Alessandra Viel, Maurizio Genuardi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

21 Citazioni (Scopus)


MUTYH-associated polyposis (MAP) is an autosomal recessive adenomatous polyposis caused by biallelic germline mutations of the base-excision-repair gene MUTYH. In MAP patients of European origin, the combined allele frequency of the mutations p.Tyr179Cys and p.Gly396Asp ranges between 50 and 82%, while these mutations have not been identified in Far Eastern Asian populations, supporting the hypothesis that a founder effect has occurred at some point in European history. To investigate the natural history of the two common European MUTYH alleles, we genotyped six gene-flanking microsatellite markers in 80 unrelated Italian and German MAP patients segregating one or both mutations and calculated their age in generations (g) by using DMLE+2.2 software. Three distinct common haplotypes, one for p.Tyr179Cys and two for p.Gly396Asp, were identified. Estimated mutation ages were 305 g (95% CS: 271-418) for p.Tyr179Cys and 350 g (95% CS: 313-435) for p.Gly396Asp. These results provide evidence for strong founder effects and suggest that the p.Tyr179Cys and p.Gly396Asp mutations derive from ancestors who lived between 5-8 thousand years and 6-9 thousand years B.C., respectively.European Journal of Human Genetics advance online publication, 30 January 2013; doi:10.1038/ejhg.2012.309.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaEuropean Journal of Human Genetics
Stato di pubblicazionePubblicato - 2013


  • founder mutation


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