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.

MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events / Aretz, Stefan; Tricarico, Rossella; Papi, Laura; Spier, Isabel; Pin, Elisa; Horpaopan, Sukanya; Cordisco, Emanuela Lucci; Pedroni, Monica; Stienen, Dietlinde; Gentile, Annamaria; Panza, Anna; Piepoli, Ada; PONZ DE LEON, Maurizio; Friedl, Waltraut; Viel, Alessandra; Genuardi, Maurizio. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - ELETTRONICO. - 22:(2014), pp. 923-929. [10.1038/ejhg.2012.309]

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

PEDRONI, Monica;PONZ DE LEON, Maurizio;
2014

Abstract

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.
2014
22
923
929
MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events / Aretz, Stefan; Tricarico, Rossella; Papi, Laura; Spier, Isabel; Pin, Elisa; Horpaopan, Sukanya; Cordisco, Emanuela Lucci; Pedroni, Monica; Stienen, Dietlinde; Gentile, Annamaria; Panza, Anna; Piepoli, Ada; PONZ DE LEON, Maurizio; Friedl, Waltraut; Viel, Alessandra; Genuardi, Maurizio. - In: EUROPEAN JOURNAL OF HUMAN GENETICS. - ISSN 1018-4813. - ELETTRONICO. - 22:(2014), pp. 923-929. [10.1038/ejhg.2012.309]
Aretz, Stefan; Tricarico, Rossella; Papi, Laura; Spier, Isabel; Pin, Elisa; Horpaopan, Sukanya; Cordisco, Emanuela Lucci; Pedroni, Monica; Stienen, Dietlinde; Gentile, Annamaria; Panza, Anna; Piepoli, Ada; PONZ DE LEON, Maurizio; Friedl, Waltraut; Viel, Alessandra; Genuardi, Maurizio
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1062783
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