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FOXO3B
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box protein O3B ==Publications== {{medline-entry |title=Genetic investigation of FOXO3A requires special attention due to sequence homology with [[FOXO3B]]. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22588664 |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. |mesh-terms=* Forkhead Box Protein O3 * Forkhead Transcription Factors * Genotype * Humans * Longevity * Phenotype * Polymorphism, Single Nucleotide * Pseudogenes * Sequence Homology |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3548564 }} {{medline-entry |title=FOXO3 gene variants and human aging: coding variants may not be key players. |pubmed-url=https://pubmed.ncbi.nlm.nih.gov/22459618 |abstract=FOXO3 is generally recognized as a "master" gene in aging since its association with longevity has been replicated in multiple organisms and human populations. A group of single nucleotide polymorphisms in linkage disequilibrium with a coding region has been associated with human longevity, but the actual functional variant is unidentified. Therefore, we sequenced the coding region in our long-lived Japanese American population in order to enhance resources for fine mapping this region. We demonstrate that of 38 published variants, 6 are misalignments with homologous nonallelic sequences from [[FOXO3B]] ([[ZNF286B]]), a pseudogene on a different chromosome; 2 are attributable to [[ZNF286B]] only, and the remaining 30 were unconfirmed, indicating that they are very rare and not likely involved in longevity. Furthermore, we identified a novel, unique, nonsynonymous coding variant in exon 3 (Gly566Ala; rs138174682) that is prevalent in multiple ethnic groups but appeared too rare for major longevity effects in our study populations. |mesh-terms=* Aged * Aged, 80 and over * Aging * Alleles * Asian Americans * Case-Control Studies * Chromosome Mapping * Cohort Studies * European Continental Ancestry Group * Female * Forkhead Box Protein O3 * Forkhead Transcription Factors * Genetic Variation * Humans * Longevity * Male * Middle Aged * Open Reading Frames * Polymorphism, Single Nucleotide * Sensitivity and Specificity |full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3668389 }}
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