Genetic investigation of FOXO3A requires special attention due to sequence homology with FOXO3B.

European Journal of Human Genetics : EJHG
Friederike FlachsbartAlmut Nebel

Abstract

Our study demonstrates that the genetic investigation of forkhead box O3A gene (FOXO3A), a validated human longevity gene, is greatly hampered by the fact that its exonic regions have 99% sequence homology with the FOXO3B pseudogene. If unaccounted for, this high degree of homology can cause serious genotyping or sequencing errors. Here, we present an experimental set-up that allows reliable data generation for the highly homologous regions and that can be used for the evaluation of assay specificity. Using this design, we exemplarily showed FOXO3A-specific results for two single-nucleotide polymorphisms (SNPs) (rs4945816 and rs4946936) that are significantly associated with longevity in our centenarian-control sample (P(each)=0.0008). Because both SNPs are located in the 3' untranslated region of FOXO3A, they could be of functional relevance for the longevity phenotype. Our experimental set-up can be used for reliable and reproducible data generation for further sequencing and genotyping studies of FOXO3A with the aim of discovering new SNPs of functional relevance.

References

Dec 2, 1993·Nature·C KenyonR Tabtiang
Mar 17, 2007·Drug Metabolism Reviews·Irma MeijermanJan H M Schellens
Sep 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bradley J WillcoxJ David Curb
Feb 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Friederike FlachsbartAlmut Nebel
May 7, 2009·Rejuvenation Research·Chiara Viviani AnselmiAnnibale Alessandro Puca
Jun 6, 2009·Aging Cell·Ludmila PawlikowskaUNKNOWN Study of Osteoporotic Fractures
Aug 4, 2009·EMBO Reports·Diana BaralleEmanuele Buratti
Sep 28, 2010·Ageing Research Reviews·Elad Ziv, Donglei Hu

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Citations

Sep 10, 2013·Age·Carolin DäumerMichael Krawczak
Sep 10, 2014·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Linda BroerJoanne M Murabito
Oct 26, 2018·Circulation Research·Cristina GiulianiClaudio Franceschi
Dec 14, 2017·Nature Communications·Friederike FlachsbartAlmut Nebel

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