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

Autor:	Aretz S; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany., Tricarico R; Department of Clinical Pathophysiology, University of Florence, Medical Genetics Unit, Florence, Italy., Papi L; Department of Clinical Pathophysiology, University of Florence, Medical Genetics Unit, Florence, Italy., Spier I; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany., Pin E; Experimental Oncology 1, Centro di Riferimento Oncologico IRCCS, Aviano, Italy., Horpaopan S; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany., Cordisco EL; Institute of Medical Genetics, Catholic University, Rome, Italy., Pedroni M; Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy., Stienen D; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany., Gentile A; Department and Laboratory of Gastroenterology, Scientific Institute and Regional General Hospital, San Giovanni Rotondo, Italy., Panza A; Department and Laboratory of Gastroenterology, Scientific Institute and Regional General Hospital, San Giovanni Rotondo, Italy., Piepoli A; Department and Laboratory of Gastroenterology, Scientific Institute and Regional General Hospital, San Giovanni Rotondo, Italy., de Leon MP; Department of Diagnostic and Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy., Friedl W; Institute of Human Genetics, University Hospital of Bonn, Bonn, Germany., Viel A; Experimental Oncology 1, Centro di Riferimento Oncologico IRCCS, Aviano, Italy., Genuardi M; 1] Department of Clinical Pathophysiology, University of Florence, Medical Genetics Unit, Florence, Italy [2] Fiorgen Foundation for Pharmacogenomics, Sesto Fiorentino, Italy.
Jazyk:	angličtina
Zdroj:	European journal of human genetics : EJHG [Eur J Hum Genet] 2014 Jul; Vol. 22 (7), pp. 923-9. Date of Electronic Publication: 2013 Jan 30.
DOI:	10.1038/ejhg.2012.309
Abstrakt:	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.
Databáze:	MEDLINE
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