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Report provided to the Human Fertilisation and Embryology Authority, April 2011 - page 7 / 45





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move and to proliferate. Mitochondrial function and replication involves both DNA contained within the mitochondria (mtDNA) and within the nucleus. The small mtDNA genome encodes 13 genes essential for the ETC, the remaining components being encoded by about 67 genes residing on chromosomes in the nucleus. The mtDNA also carries transfer RNA (tRNA) genes required for mitochondrial protein synthesis. Mitochondria have other important roles in cellular physiology, notably in programmed cell death (apoptosis) and steroid synthesis, although these depend on genes encoded entirely within the nucleus.

    • 2.2

      Mutations in any of the 1500 nuclear genes required for mitochondrial function can lead to severe disease. These mutations are inherited in the same way as any other nuclear genetic traits. About 1 in 5000 births, and a likely higher proportion of fetuses, has a mtDNA mutation. The inheritance and regulation of mtDNA, however, is different from genetic information that is located on chromosomes within the nucleus of the cell. There are several compounding reasons for this:

      • 2.2.1

        Maternal inheritance: mtDNA is transmitted solely from the mother via the cytoplasm of the oocyte1. In contrast, nuclear genes, apart from genes specific to the X and Y chromosomes, are inherited both maternally and paternally (one copy from the mother and one from the father).

2.2.2 mtDNA copy number: The number of mitochondria varies dramatically between cell types during different stages of development. Adult (somatic) cells typically contain from a few hundred to several thousand mitochondria and this generally reflects demand for ATP in these cells. Tissues, such as muscle and brain, therefore have high numbers of mitochondria, and it is these tissues that tend to show the strongest phenotypes when mitochondria are defective. The numbers of mitochondria in the germ line varies according to the stage of development; thus oocytes have more than 100,000, each cell of a blastocyst has about 1000, and there may be as few as 10 per primordial germ cell

1 Sperm contain an active mitochondrion, which is essential for their motility, but this is programmed for destruction immediately after fertilisation. There have been very rare cases noted where paternal mitochondria have persisted naturally, or after certain somatic cell nuclear transfer experiments, but these are sufficiently exceptional that the panel does not consider this to be a significant issue.

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