Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission.
Variation in germline mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission.
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DOI：
10.1038/ng.2427
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发表时间：
2012-11
期刊：
影响因子：
30.8
通讯作者：
Chinnery, Patrick F.
中科院分区：
文献类型：
--
作者：
Freyer, Christoph;Cree, Lynsey M.;Mourier, Arnaud;Stewart, James B.;Koolmeister, Camilla;Milenkovic, Dusanka;Wai, Timothy;Floros, Vasileios I.;Hagstrom, Erik;Chatzidaki, Emmanouella E.;Wiesner, Rudolf J.;Samuels, David C.;Larsson, Nils-Goeran;Chinnery, Patrick F.
遗传瓶颈解释了在致病性突变的传播过程中观察到的线粒体DNA（mtDNA）异质性的显著变化，但确切的时间仍然存在争议，并且尚不清楚选择是否起作用。这些问题对于未来母亲的遗传咨询和开发旨在预防疾病的治疗方法至关重要。通过研究小鼠线粒体tRNAMet基因中异质性单碱基对缺失的传递，我们发现哺乳动物mtDNA异质性水平主要是在产前发育中的雌性生殖系中确定的。虽然我们没有看到产前mtDNA选择的证据，但在下一代的后代中观察到了偏斜的异质性水平，这与纯化选择一致。高百分比水平的tRNAMet突变与整体线粒体RNA的补偿性增加有关，改善了生化表型，并解释了为什么生殖力不受影响。
A genetic bottleneck explains the marked changes in mitochondrial DNA (mtDNA) heteroplasmy observed during the transmission of pathogenic mutations, but the precise timing remains controversial, and it is not clear whether selection plays a role. These issues are critically important for the genetic counseling of prospective mothers, and developing treatments aimed at disease prevention. By studying mice transmitting a heteroplasmic single base-pair deletion in the mitochondrial tRNAMet gene, we show that mammalian mtDNA heteroplasmy levels are principally determined prenatally within the developing female germ line. Although we saw no evidence of mtDNA selection prenatally, skewed heteroplasmy levels were observed in the offspring of the next generation, consistent with purifying selection. High percentage levels of the tRNAMet mutation were linked to a compensatory increase in overall mitochondrial RNAs, ameliorating the biochemical phenotype, and explaining why fecundity is not compromised.
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影响因子：
9.8
作者：
Brown, DT;Samuels, DC;Chinnery, PF
通讯作者：
Chinnery, PF
影响因子：
29
作者：
Camara, Yolanda;Asin-Cayuela, Jorge;Larsson, Nils-Goran
通讯作者：
Larsson, Nils-Goran
影响因子：
56.9
作者：
Fan, Weiwei;Waymire, Katrina G.;Wallace, Douglas C.
通讯作者：
Wallace, Douglas C.
影响因子：
64.8
作者：
OLIVO, PD;VANDEWALLE, MJ;HAUSWIRTH, WW
通讯作者：
HAUSWIRTH, WW
影响因子：
30.8
作者：
Cao, Liqin;Shitara, Hiroshi;Yonekawa, Hiromichi
通讯作者：
Yonekawa, Hiromichi