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This finding comes from a research article title "Rate of de novo mutations and the importance
of father's age to disease risk". it was published in August 2012 in Nature by Stefansson's group
at the university of iceland in reykjavik.
This finding deals with our DNA and how our DNA differs from our parent's DNA. Let's examine
this a little closer by looking at HOW DNA is transmitted from parents to children. We
inherit half of our DNA from our mother and half of our DNA from our father. The DNA from
our mother is provided in the egg and the DNA from our father is provided in the ***
which together with the egg makes the embryo. This is simple to understand but the story
of how we get our DNA sequence gets a little more complicated.
We know that as women age, the egg can, by mistake, give to the child a different DNA
sequence than that of the mother. This is called a "mutation" which is a change in the
DNA sequence. Mutations in the egg provided by the mother as the mother ages is the reason
women over 35 are at increased risk of having a child with Down Syndrome.
Mutations in eggs or *** can cause a child to inherit a piece of DNA sequence that is
found in neither the mother nor the father. We call this a "de novo" mutation.
As of now, it was not known precisely if the father also provided DNA with de novo mutations
to the child or if all of the de novo mutations came from the mother. In this finding, the
scientists were interested in seeing if fathers also contributed de novo mutations to the
child and if age at time of conception had any effect on the number of mutations the
father passed on to his child.
To do this, the scientists used 78 trios which include two parents and a child from the Icelandic
population. Iceland is a great place to perform genetic studies because there has been very
little migration into and out of Iceland so individuals in Iceland all have very similar
DNA. This makes it easier for scientists to find mutations or differences in the DNA sequence.
So the scientists took the DNA of these 78 trios and sequenced all of the DNA looking
for specific changes in the DNA sequence at single bases. And what they found was very
interesting! The scientists found that the children had mutations that were not present
in either one of the parents. This meant that one of the two parents had transmitted DNA
that was mutated to the child and this happened either in the egg or in the ***. By looking
at the DNA sequence around the mutation, the scientists were able to say that fathers were
transmitting to their children 4 times as many mutations as the mothers were. PAUSE
But that's not all! When the scientists took into account father's age at the time of conception,
they found that the older the father, the more mutations were passed onto the child:
(pause) two mutations were passed on to the child for every year of the father's age at
the time of conception. So if the father was 22 years old when the child was conceived
then he passed on about 44 mutations to his child, and the mother only passed on about
10 mutations (or 4 times fewer than the father). The data also indicated that the older the
father at the time of conception, the higher the mutation rate at ages above 40. So if
the father was 40 at the age of the conception, then he would pass on more than 2 mutations
per year of his life ( more than 80 mutations)! so the mutation rate per year of the father's
life seemed to increase EXPONENTIALLY as the father ages. Some of the older fathers that
were studied here had passed on more than 100 mutations to their child!!
So what do all of these mutations mean when it comes to the health of the child? Are they
good or are they bad? Mutations are often thought of as being detrimental and they in
fact can cause disease and this happens most often BUT mutations can also be beneficial
by protecting you from illness. So are these de novo mutations transmitted by the father
detrimental to the child's health? Or are they beneficial?
Population studies in Iceland have shown that schizophrenia and autism increase significantly
with father's age at conception. This is in line with the results of this finding showing
that fathers transmit more mutations to their children with increasing age at the time of
conception. So this suggests that at least some of the mutations that are transmitted
from father to child may be detrimental and increase the risk of autism and schizophrenia.
This does not mean that all of the mutations are detrimental. it's definitely possible
that some of the mutations may be beneficial to the child but this remains an open question.
So what did this study show?
Thanks to new and affordable techniques for sequencing DNA, this study was able to show
that :
fathers transmit a considerable number of SINGLE BASE mutations to their child, about
4 times more than mothers. In addition, this study also showed that the number of mutations
transmitted by the father increases as the father ages at a rate of about 2 mutations
per year of the father's age at time of conception and this may be increase exponentially at
above 40 years of age.
It is very surprising that father's transmit so many mutations to their child and that
the number of mutations transmitted increases with father's age! Before this finding, it
was known that father's transmitted SOME mutations to their child but it was thought that those
mutations transmitted by the father were insignificant compared to the mutations transmitted by the
mother. But this study clearly shows that this is NOT the case!!
It still remains to be seen exactly HOW those mutations transmitted by the father affect
the child's health and how this might shape the population's genetic pool. As our population
ages and men conceive children later in life, it is interesting to think about this study
in the context of the population as a whole to try to predict or anticipate if certain
diseases will be more prevalent due to these mutations. On the other hand, these de novo
mutations may provide an advantage and allow us to continuously adapt to our ever-changing
environment by providing more genetic variation.