@article{Ye2013, abstract = {It has been postulated that aging is the consequence of an accelerated accumulation of somatic DNA mutations and that subsequent errors in the primary structure of proteins ultimately reach levels sufficient to affect organismal functions. The technical limitations of detecting somatic changes and the lack of insight about the minimum level of erroneous proteins to cause an error catastrophe hampered any firm conclusions on these theories. In this study, we sequenced the whole genome of DNA in whole blood of two pairs of monozygotic (MZ) twins, 40 and 100 years old, by two independent next-generation sequencing (NGS) platforms (Illumina and Complete Genomics). Potentially discordant single-base substitutions supported by both platforms were validated extensively by Sanger, Roche 454, and Ion Torrent sequencing. We demonstrate that the genomes of the two twin pairs are germ-line identical between co-twins, and that the genomes of the 100-year-old MZ twins are discerned by eight confirmed somatic single-base substitutions, five of which are within introns. Putative somatic variation between the 40-year-old twins was not confirmed in the validation phase. We conclude from this systematic effort that by using two independent NGS platforms, somatic single nucleotide substitutions can be detected, and that a century of life did not result in a large number of detectable somatic mutations in blood. The low number of somatic variants observed by using two NGS platforms might provide a framework for detecting disease-related somatic variants in phenotypically discordant MZ twins.}, author = {Ye, Kai and Beekman, Marian and Lameijer, Eric-Wubbo and Zhang, Yanju and Moed, Matthijs H. and van den Akker, Erik B. and Deelen, Joris and Houwing Duistermaat, Jeanine J. and Kremer, Dennis and Anvar, Seyed Yahya and Laros, Jeroen F. J. and Jones, David and Raine, Keiran and Blackburne, Ben and Potluri, Shobha and Long, Quan and Guryev, Victor and van der Breggen, Ruud and Westendorp, Rudi G. J. and C 't Hoen, Peter A. and ‘t Hoen, Peter A. C. and Dunnen, Johan den and den Dunnen, Johan and van Ommen, Gert Jan B. and Willemsen, Gonneke and Pitts, Steven J. and Cox, David R. and Ning, Zemin and Boomsma, Dorret I. and Eline Slagboom, P. and Slagboom, P. Eline}, doi = {10.1017/thg.2013.73}, journal = {Twin Research and Human Genetics}, month = {nov}, pages = {1026-1032}, title = {Aging as Accelerated Accumulation of Somatic Variants: Whole-Genome Sequencing of Centenarian and Middle-Aged Monozygotic Twin Pairs}, url = {https://www.researchgate.net/profile/Marian_Beekman/publication/258250392_Aging_as_Accelerated_Accumulation_of_Somatic_Variants_Whole-Genome_Sequencing_of_Centenarian_and_Middle-Aged_Monozygotic_Twin_Pairs/links/00b495280efd147aa7000000.pdf}, volume = {16}, year = {2013} }