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In Huge Shock, Mitochondrial DNA Can Be Inherited From Fathers

Discussion in 'Histology' started by Nada El Garhy, Nov 26, 2018.

  1. Nada El Garhy

    Nada El Garhy Golden Member

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    ONE OF THE MOST FUNDAMENTAL THINGS WE THOUGHT WE KNEW ABOUT MITOCHONDRIA, THE POWERHOUSES OF CELLS, TURNS OUT TO NOT ALWAYS BE TRUE.

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    A piece of high school genetics, relied on for many sorts of genetic testing, has been found to have exceptions. Although mitochondrial DNA (mtDNA) is normally received from the mother, three families have been identified where people received some of their mtDNA, three-quarters in the most extreme case, from their father. The finding may change the way we treat mitochondrial diseases and brings genetic testing for maternal ancestry into question.

    MtDNA exists separately from the rest of our DNA, inside the thousands of mitochondria within each cell, rather than the cell nucleus. It is so widely accepted as being from the mother's side it is sometimes known as the Eve Gene, the idea being that it can be traced back to some primeval mother of all living humans. Testing of mtDNA is used to identify maternal ancestry.

    However, all that will have to change after Dr Shiyu Luo of the Cincinnati Children's Hospital Medical Center published a paper in the Proceedings of the National Academy of Sciences.

    Luo's first exception is a boy who at four was hospitalized with symptoms suggestive of mitochondrial disease. Sequencing of the boy's mitochondria revealed no disease-causing genes, but some oddities in the mtDNA that led Luo and colleagues to sequence other family members for comparison. Around 40 percent of the boy's mitochondria matched that from his mother's father, and only 60 percent came from his grandmother.

    After testing of other members of the same family, and other families with mitochondrial diseases, Luo found that, while paternal inheritance is very rare, it has occurred at least 17 times in three tested families.

    Embryos receive mtDNA from both parents, just as occurs with the rest of their genome, but the father's mtDNA is eliminated long before birth. The process that drives this elimination is not well understood, presumably a prerequisite for learning what is different in these cases. Nevertheless, the fact that paternal DNA apparently runs in families led Luo to propose that an abnormality in a nuclear DNA gene is responsible.

    Mutant mitochondrial genes are quite common, often co-existing within cells with healthy versions. They cause a range of serious diseases, with the severity determined by the proportion of mitochondria carrying the mutant gene. A woman with such low levels of bad mitochondria that she shows few or no symptoms may pass on a larger dose to her children, with serious consequences. Efforts to avoid these have led to so-called “three-parent babies”, recently legalized in the UK.

    Mitochondria are often referred to as cells' power supplies, providing the energy needed to keep us running by producing the energy-carrying molecule ATP. They also serve other functions, such as triggering cell death when necessary. They're thought to have once been independently living prokaryotic cells that formed a symbiotic relationship with eukaryotes, and eventually became incorporated.

    Human mitochondria are programmed by just 37 genes, with less than 17,000 base pairs, compared to 3 billion for our entire genome. This fact, combined with the frequency of mitochondrial genetic diseases, led to this being the first substantial part of the human genome to be sequenced, back when that was a very hard thing to do.

    Some plants, algae, and yeast get their mtDNA from their fathers, but the relevance to humans is questionable. Cases of partially paternal mtDNA have been seen in fruit flies, and more relevantly mice and sheep. Claims of paternal mtDNA inheritance have been made before, but most turned out to have been errors caused by mislabeling of samples or contamination in the lab. Reflecting the extraordinary nature of her claims, Luo had all sequencing independently conducted at two labs using different techniques and separate blood samples.

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