Heteroplasmic segregation associated with trisomy-9 in cultured human cells.

S K Lehtinen, J N Spelbrink, H T Jacobs
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引用次数: 3

Abstract

In cybrid cells carrying the mitochondrial A3243G MELAS mutation, which were also heteroplasmic for the G12300A suppressor mutation, we observed a transient episode of heteroplasmic instability, resulting in a wide diversification in G12300A heteroplasmy levels and a shift in the average heteroplasmy level from 11 to 29%. These cells were found to be trisomic for chromosome 9, whereas a minority of cells that retained disomy-9 showed no instability. Coculture experiments implied that trisomy-9 cells exhibited a significant growth advantage, but neither heteroplasmy levels, respiratory phenotype nor trisomy-9 itself had direct selective value under standard culture conditions. Mitochondrial nucleoid number was the same (50-100) in cells that had or had not experienced transient heteroplasmic instability, but 1-2 orders of magnitude less than the segregation number in such cells. These findings support the idea that mtDNA partition is under nuclear genetic control, and implicate a locus on chromosome 9 in this regulation.

培养的人类细胞中与9三体相关的异质分离。
在携带线粒体A3243G MELAS突变(G12300A抑制突变也是异质性突变)的杂交细胞中,我们观察到异质性不稳定的短暂事件,导致G12300A异质性水平的广泛多样化,平均异质性水平从11%转移到29%。这些细胞被发现是9号染色体的三体,而少数保留9号二体的细胞没有表现出不稳定性。共培养实验表明,三体-9细胞表现出显著的生长优势,但在标准培养条件下,异质性水平、呼吸表型和三体-9本身都不具有直接的选择价值。在有或没有经历过短暂异质性不稳定的细胞中,线粒体类核数相同(50-100),但比这种细胞中的分离数少1-2个数量级。这些发现支持了mtDNA分裂受核遗传控制的观点,并暗示9号染色体上的一个位点参与了这一调控。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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