Inheritance

In mammal species, mitochondria are inherited from the mother (FDA, 2014). While sperm do have mitochondria on their way to the ovum, these mitochondria are degraded through a process known as ubiquitination, proteolytic destruction of the male mitochondria once the sperm has fertilized the egg (Sutovsky et al., 2000).

Thus, the mitochondrial genome is solely inherited through the maternal line. While the inheritance patterns of mitochondria vary amongst every individual, there are two main transmission patterns that refer to the mitochondria passed from mother to offspring. The first is known as homoplasmy. If a mother is homoplasmic, she has a single variant of mtDNA. Thus, all her oocytes will receive the same mtDNA and her offspring will inherit the identical mtDNA (FDA, 2014). The other pattern is known as heteroplasmy, and it introduces a more complicated picture of mtDNA inheritance.

Heteroplasmy results when a mother has multiple variations in her mtDNA. This variation can cause unequal partitioning of healthy versus mutant mtDNA that is passed on from mother to child. This phenomenon is known as a mitochondrial bottleneck. It refers to the situation in which a small number of mtDNAs can be over-represented in subsequent children because the mitochondria is passed down preferentially and due to the small sample size that was induced by the bottleneck (FDA, 2014).

The phenomenon of heteroplasmy and mitochondrial bottleneck effect plays a major role in the ability to predict a mother’s likelihood of transmitting mitochondrial disease to her children. Clinical screening loses its ability to predict the likelihood because a mother may pass on large or small amounts of mutant mtDNA (FDA, 2014). Furthermore, due to the heteroplasmy of mitochondria present in the female egg, mitochondrial replacement could also inadvertently introduce small amounts of mutant mtDNA into the resulting embryo.

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