The Complete Genome Sequences, Unique Mutational Spectra, and Developmental Potency of Adult Neurons Revealed by Cloning

Jennifer L. Hazen, Gregory G. Faust, Alberto R. Rodriguez, William C. Ferguson, Svetlana Shumilina, Royden A. Clark, Michael J. Boland, Greg Martin, Pavel Chubukov, Rachel K. Tsunemoto, Ali Torkamani, Sergey Kupriyanov, Ira M. Hall, Kristin K. Baldwin

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Somatic mutation in neurons is linked to neurologic disease and implicated in cell-type diversification. However, the origin, extent, and patterns of genomic mutation in neurons remain unknown. We established a nuclear transfer method to clonally amplify the genomes of neurons from adult mice for whole-genome sequencing. Comprehensive mutation detection and independent validation revealed that individual neurons harbor ~100 unique mutations from all classes but lack recurrent rearrangements. Most neurons contain at least one gene-disrupting mutation and rare (0-2) mobile element insertions. The frequency and gene bias of neuronal mutations differ from other lineages, potentially due to novel mechanisms governing postmitotic mutation. Fertile mice were cloned from several neurons, establishing the compatibility of mutated adult neuronal genomes with reprogramming to pluripotency and development.

Original languageEnglish
Pages (from-to)1223-1236
Number of pages14
JournalNeuron
Volume89
Issue number6
DOIs
StatePublished - Mar 16 2016

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    Hazen, J. L., Faust, G. G., Rodriguez, A. R., Ferguson, W. C., Shumilina, S., Clark, R. A., Boland, M. J., Martin, G., Chubukov, P., Tsunemoto, R. K., Torkamani, A., Kupriyanov, S., Hall, I. M., & Baldwin, K. K. (2016). The Complete Genome Sequences, Unique Mutational Spectra, and Developmental Potency of Adult Neurons Revealed by Cloning. Neuron, 89(6), 1223-1236. https://doi.org/10.1016/j.neuron.2016.02.004