As described in this chapter, mothers will pass on a mitochondrial defect to their offspring. In a type of gene therapy, one approach to circumvent this problem is to have two different maternal contributions, with the nucleus of the female with the defective mitochondria being placed in an enucleated egg derived from a female with normal mitochondria. After fertilization, the resulting offspring would have three parental sources of DNA—with nuclear DNA derived from a mother and a father, and mitochondrial DNA derived from another 'mother.' Recently, children with this genetic makeup have been born, but the elimination of defective mitochondria is not complete, with the amount of defective mitochondria derived from the defective mother ranging from 0 to 9%. Discuss potential complications resulting from such a mixture of genomes.

Key Concepts

Mitochondrial Inheritance

Mitochondrial inheritance refers to the transmission of genetic material located in mitochondria, which is exclusively passed from mothers to their offspring. This type of inheritance is significant because mutations in mitochondrial DNA can lead to various metabolic disorders. Understanding this concept is crucial for analyzing how mitochondrial defects can affect offspring and the implications of using alternative mitochondrial sources in gene therapy.

Gene Therapy

Gene therapy is a technique that modifies or manipulates genes to treat or prevent disease. In the context of mitochondrial defects, gene therapy can involve replacing defective mitochondrial DNA with healthy mitochondrial DNA from a donor. This approach aims to reduce the impact of inherited mitochondrial diseases, but it raises ethical and biological questions regarding the long-term effects and stability of the introduced genetic material.

Genomic Imprinting and Epigenetics

Genomic imprinting is a genetic phenomenon where certain genes are expressed in a parent-of-origin-specific manner, influenced by epigenetic factors. In cases where offspring have genetic contributions from multiple maternal sources, the interaction between these imprinted genes can lead to unexpected developmental outcomes. Understanding imprinting and epigenetics is essential for assessing potential complications arising from the mixing of genomes in offspring with three parental DNA sources.