GENEALOGY-DNA-L ArchivesArchiver > GENEALOGY-DNA > 2006-11 > 1163463232
From: "Roger Rines" <>
Subject: Re: [DNA] Question about mitochondrial birth defects
Date: Mon, 13 Nov 2006 16:13:52 -0800
Dora Smith asked:
> Question. See this week's reason to be terrified of life in the current
> issue of Time magazine.
> Article is primarily about dramatic deadly diseases caused by genetically
> defective mitochondria.
> Now, I'm checking. Is it possible for mitochondria to mutate that
> dramatically from one generation to the next, such that a baby can die of
> wasting mitochondrial disease and the mother has no health issues?
> I mean, does all mitochondrial DNA mutate very slowly over tens of
> of years, or just the markers used for DNA analysis? If the former, then
> the scenario presented in Time magazine is not possible, or atleast is so
> unlikely there's no reason to play it up in Time magazine's reason of hte
> week to be terrified of life.
I found your question interesting enough to send your query on to my son, a
principle investigator at a genomic institute.
Here is what he had to say:
Yes, the media loves to publicize these kinds of stories.
As for the lethal mutation in one generation being passed on to the next,
the answer is yes. Here is an example involving cystic fibrosis.
Until recently, children inheriting this disease are lucky to live into
their mid-20s. Let's say you and mom carry a single mutation for cystic
fibrosis and both you and mom also have one normal gene for cystic fibrosis.
You and mom don't demonstrate any cystic fibrosis problems because the one
good copy "works well enough" to keep you healthy. However, you had 3
children...we each had a 25% chance of having cystic fibrosis because each
one of us could have inherited both defective copies of the gene. We also
had a 50% chance of inheriting only 1 mutant copy. In other words, we had a
75% chance of inheriting AT LEAST 1 bad copy of the gene but ONLY a 25% of
having cystic fibrosis. It is a numbers game...good thing you didn't a
forth kid, huh?
Same thing has probably happened in this article. The older kid probably
inherited at least 1 normal copy of the gene while the younger kid was
unfortunate enough to get both bad ones (from mom and dad). The confusing
part of the article (e.g. bad writing), is that the author makes you think
that the mom is "solely responsible" for carrying the disease since she is
responsible for donating the mitochondrial (MT) DNA. However, it is more
likely that both the mom and the dad carry a bad copy of the gene. 1500
mitochondrial genes are carried in our genomic DNA, not our MT DNA. Both
mom and dad carry genes for mitochondrial function. If the mitochondrial
gene was only encoded in the MT-DNA, then the mom would probably have the
disease as well. They confuse the reader by talking about the MT-DNA when
in actuality it is more likely that the mutant gene is carried in the
genomic DNA. The real problem is our inability to diagnose mitochondrial
diseases. Those little buggers are very important, but very difficult to
If you aren't confused yet, well keep reading. There are more situations
where it is possible that a disease could be inherited from just the mom.
There is a genetic situation known as redundancy. Quite often, if a protein
is very important, then there are usually several different copies in our
genome. This happens because parts of the genome have been over-replicated
and maintained throughout evolution. Now for the confusing part, if we
carry the same copy of the mitochondrial gene in the MT-DNA and in the
genomic DNA, then it is possible to have 1 bad copy in the MT-DNA, as well
as 1 bad and 1 good copy in the genomic DNA. Now, the mom has a kid, but
only passes on the 1 bad copy of the genomic DNA and the 1 bad copy in all
her mitochondrial-DNA...bam...the kid inherits a disease (that could be
lethal) and the mom never showed symptoms because she always had at least 1
good copy masking the disease. This situation is unlikely but a
Still with me? Good, because it can actually be even more complex than this
when you consider that many proteins work together in large complexes and
the severity of a disease could be based on synergistic effects, the "does
not work well enough" situation. There is also a genetic situation known as
"suppressors" where one mutation masks another mutation. But we'll save
this for another day.
Hopefully, this answers your question more than confusing you. I could
explain it much better in person but I'm procrastinating on another project
right now so this was a fun distraction. ;)
It sure has been helpful having smart kids in the family. :D
|Re: [DNA] Question about mitochondrial birth defects by "Roger Rines" <>|