Cambridge University. UK: New research reveals that the sperm cells of adolescent boys have more than six times the rate of DNA mutations as the equivalent egg cells in adolescent girls, resulting in higher rates of DNA mutation being passed down to children of teenage fathers. The findings suggest that the risk of birth defects is higher in the children of teenage fathers as a consequence.
A
genetic study of over 24,000 parents and their children has shown that
the children of teenage fathers have unexpectedly high levels of DNA
mutations.
Mutations, the result of DNA copying errors during cell division, can
occur in different cells of the body and at different times during
life. Some, such as those that occur in 'germ cells' – which create
sperm or eggs – cause changes affecting the individual's offspring.
Previously, it was thought that germ cells in both boys and girls go
through a similar number of cell divisions, and should have roughly the
same rates of DNA mutation by the time an individual reaches puberty.
Now, a new study shows that the number of cell divisions – and
consequently DNA mutation rates – experienced by the germ cells of
teenage boys is six times higher than for those of girls, and that DNA
mutations passed down to the children of teenage fathers are higher as a
result.
Researchers say the increased DNA mutations in the reproductive cells
of adolescent boys could explain why the children of teenage fathers
have a higher risk for disorders such as autism, schizophrenia and spina
bifida.
Men produce germ cells throughout their lives, and it was previously
assumed that DNA mutation in germ cells increased as men get older –
more cell division and greater DNA mutation has occurred as men age.
However, the latest results show that the germ cells of adolescent boys are an exception to this aging rule.
Researchers have shown that male germ cells go through around 150
cell divisions by puberty, compared to the 22 cell divisions experienced
by female oocytes (immature egg cells). This raises in tandem the rates
of DNA mutation incurred by cell division in the germ cells of teenage
boys – creating higher chances of hereditary disease in children
conceived by adolescent fathers.
The researchers say that this could be the result of unknown cell
divisions during male childhood or a spike in DNA error during puberty –
although the reasons are currently unclear.
Prior to the new findings, male germ cells were thought to undergo 30
divisions by puberty. The results overturn previous notions that the
younger the man, the less cell division and the less risk of DNA
mutations in germ – and later sperm – cells.
In fact, researchers say that – while more work needs to be done –
these initial findings furthermore indicate that sperm cells in
teenagers have approximately 30% higher rates of DNA mutation than those
of young men in their twenties, and that teenage boys have similar
levels of DNA mutation in their sperm cells to men aged in their late
thirties and forties.
“It appears that the male germ cells accumulate DNA errors unnoticed
during childhood, or commit DNA errors at an especially high level at
the onset of puberty. However, the reason for this is not yet clear,”
said geneticist Dr Peter Forster, a Fellow of Murray Edwards College and
the McDonald Institute at the University of Cambridge, who conducted
the study with colleagues from the Institute of Forensic Genetics in
Münster, Germany.
“Possibly the DNA copying mechanism is particularly error-prone at
the beginning of male puberty. Or, sperm production in boys may undergo
dozens more cell cycles – and therefore DNA copying errors – than has
previously been suspected,” he said.
Either way, the textbooks may well need to be rewritten as a result
of the new findings, says Forster, which are published today in the
journal Proceedings of the Royal Society B.
The research team used DNA from blood and saliva samples taken from
24,097 normal parents and their validated biological children from areas
of Germany, Austria, the Middle East and West Africa.
The researchers analysed a type of DNA known as ‘microsatellites’ –
simple, repetitive sequences of DNA that only mutate as a result of cell
replication, providing the team with a natural ‘cell-cycle counter’
which they used to track the number of times a cell divides, and
consequently the rate of mutations through DNA copying error.
Through comparative analysis, the research team discovered the
increased DNA mutations in children of teenage fathers, and that
mutations are six times higher in male sperm cells during onset of
puberty than in female oocytes.
While this means that the children of teenage fathers have increased
chance of abnormality, Forster points out that the risk is still very
small: perhaps around 2% as opposed to a general average abnormality
risk of 1.5%.
The team hope to develop the cell-cycle counter technique used in the
study and apply it to cancers, in order to better estimate the age of
such conditions in individuals, and the number of cell divisions between
the initial cellular malfunction and tumour growth.
- See more at:
http://www.cam.ac.uk/research/news/study-finds-increased-dna-mutations-in-children-of-teenage-fathers#sthash.oa1CLIRR.dpuf