Polar Body Genome Transfer for Preventing the Transmission of Inherited Mitochondrial Diseases

作者: Tian Wang , Hongying Sha , Dongmei Ji , Helen L. Zhang , Dawei Chen

DOI: 10.1016/J.CELL.2014.04.042

关键词:

摘要: Inherited mtDNA diseases transmit maternally and cause severe phenotypes. Currently, there is no effective therapy or genetic screens for these diseases; however, nuclear genome transfer between patients' healthy eggs to replace mutant mtDNAs holds promises. Considering that a polar body contains few mitochondria shares the same genomic material as an oocyte, we perform prevent transmission of variants. We compare effects different types germline transfer, including spindle-chromosome pronuclear first second in mice. Reconstructed embryos support normal fertilization produce live offspring. Importantly, analysis confirms F1 generation from possesses minimal donor carryover compared other procedures. Moreover, genotype remains stable F2 progeny after transfer. Our preclinical model demonstrates has great potential inherited diseases.

参考文章(55)
Masahito Tachibana, Paula Amato, Michelle Sparman, Joy Woodward, Dario Melguizo Sanchis, Hong Ma, Nuria Marti Gutierrez, Rebecca Tippner-Hedges, Eunju Kang, Hyo-Sang Lee, Cathy Ramsey, Keith Masterson, David Battaglia, David Lee, Diana Wu, Jeffrey Jensen, Phillip Patton, Sumita Gokhale, Richard Stouffer, Shoukhrat Mitalipov, Towards germline gene therapy of inherited mitochondrial diseases Nature. ,vol. 493, pp. 627- 631 ,(2013) , 10.1038/NATURE11647
Eric A. Schon, Salvatore DiMauro, Michio Hirano, Human mitochondrial DNA: roles of inherited and somatic mutations Nature Reviews Genetics. ,vol. 13, pp. 878- 890 ,(2012) , 10.1038/NRG3275
Rebecca Sanders, Jim F. Huggett, Claire A. Bushell, Simon Cowen, Daniel J. Scott, Carole A. Foy, Evaluation of digital PCR for absolute DNA quantification. Analytical Chemistry. ,vol. 83, pp. 6474- 6484 ,(2011) , 10.1021/AC103230C
Irene Cantone, Amanda G Fisher, Epigenetic programming and reprogramming during development. Nature Structural & Molecular Biology. ,vol. 20, pp. 282- 289 ,(2013) , 10.1038/NSMB.2489
Emma L. Blakely, John W. Yarham, Charlotte L. Alston, Kate Craig, Joanna Poulton, Charlotte Brierley, Soo‐Mi Park, Andrew Dean, John H. Xuereb, Kirstie N. Anderson, Alistair Compston, Chris Allen, Saba Sharif, Peter Enevoldson, Martin Wilson, Simon R. Hammans, Douglass M. Turnbull, Robert McFarland, Robert W. Taylor, Pathogenic Mitochondrial tRNA Point Mutations: Nine Novel Mutations Affirm Their Importance as a Cause of Mitochondrial Disease Human Mutation. ,vol. 34, pp. 1260- 1268 ,(2013) , 10.1002/HUMU.22358
Nadine Gigarel, Laetitia Hesters, David C. Samuels, Sophie Monnot, Philippe Burlet, Violaine Kerbrat, Frédéric Lamazou, Alexandra Benachi, René Frydman, Josué Feingold, Agnes Rotig, Arnold Munnich, Jean-Paul Bonnefont, Nelly Frydman, Julie Steffann, Poor Correlations in the Levels of Pathogenic Mitochondrial DNA Mutations in Polar Bodies versus Oocytes and Blastomeres in Humans American Journal of Human Genetics. ,vol. 88, pp. 494- 498 ,(2011) , 10.1016/J.AJHG.2011.03.010
Teresa Almeida Santos, Shahy El Shourbagy, Justin C. St. John, Mitochondrial content reflects oocyte variability and fertilization outcome Fertility and Sterility. ,vol. 85, pp. 584- 591 ,(2006) , 10.1016/J.FERTNSTERT.2005.09.017
Vivien Marx, PCR: paths to sensitivity Nature Methods. ,vol. 11, pp. 241- 245 ,(2014) , 10.1038/NMETH.2849