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

Maurizio Genuardi, S Aretz, R Tricarico, L Papi, L Spier, E Pin, S Horpaopan, L Lucci Cordisco, M Pedroni, D Stienen, A Gentile, A Panza, A Piepoli, Mp De Leon, W Friedl, A. Viel

Risultato della ricerca: Contributo in rivistaArticolo in rivista

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
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaEuropean Journal of Human Genetics
DOI
Stato di pubblicazionePubblicato - 2013

Keywords

  • MUTYH-associated polyposis

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