Basic Human Genetics Nov 29, 2018 18:12:06 GMT
Post by Admin on Nov 29, 2018 18:12:06 GMT
The research, published in the Proceedings of the National Academy of Sciences, showed conclusively that, in three unrelated families, mitochondria from the father’s sperm had been passed to the children over several generations.
Overturning scientific understanding about this fundamental truth, opens the possibility for better treatment of mitochondrial disorders, which blight many families with devastating disease.
Most of a cell’s DNA is contained in its nucleus but mitochondria sit separately inside the cell and have their own DNA. This is because mitochondria are thought to have started as separate organisms, which entered early cells about 1.45 billion years ago and never left. They reproduce themselves and move from one generation to another by ‘hitching a lift’ in the egg.
During fertilization, the father’s sperm transfers his DNA into an egg, but few or none of the sperm’s mitochondria get in. If any do, then there are mechanisms designed to destroy them.
The new research found that, in a small number of families, the mitochondria from the father that found its way into the egg were not destroyed, though we don’t yet know enough to say why.
There was also some evidence this mitochondrial DNA from the father may have then been copied as the fertilized egg grew into an embryo even more than that from the mother.
The energy-producing organelle mitochondrion contains its own compact genome, which is separate from the nuclear genome. In nearly all mammals, this mitochondrial genome is inherited exclusively from the mother, and transmission of paternal mitochondria or mitochondrial DNA (mtDNA) has not been convincingly demonstrated in humans. In this paper, we have uncovered multiple instances of biparental inheritance of mtDNA spanning three unrelated multiple generation families, a result confirmed by independent sequencing across multiple unrelated laboratories with different methodologies. Surprisingly, this pattern of inheritance appears to be determined in an autosomal dominantlike manner. This paper profoundly alters a widespread belief about mitochondrial inheritance and potentially opens a novel field in mitochondrial medicine.
Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.
PNAS published ahead of print November 26, 2018