Maternal Inheritance

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
Nikki2019
Contributor
Contributor
Posts: 23
Joined: Mon Dec 17, 2018 10:24 pm

Maternal Inheritance

Postby Nikki2019 » Fri Jan 11, 2019 12:42 pm

I came across some reading which states that a "mutation in the DNA of the mitochondria of the cytochrome C oxidase gene" means that if mom passed it on you than you are 9 times more likely than if dad did? Do you think this is just based on a small study ?

User avatar
slacker
Mod
Mod
Posts: 1651
Joined: Wed Aug 03, 2016 6:20 pm
Location: Louisville KY

Re: Maternal Inheritance

Postby slacker » Fri Jan 11, 2019 2:48 pm

Nikki2019 wrote:I came across some reading which states that a "mutation in the DNA of the mitochondria of the cytochrome C oxidase gene" means that if mom passed it on you than you are 9 times more likely than if dad did? Do you think this is just based on a small study ?


Humans inherit their mitochondria from mom alone, with rare exceptions according to this wiki entry. So without reading the study you mention, I'm not sure what it meant by 9x more likely if passed to you through mom...
Slacker
E4/E4

Nikki2019
Contributor
Contributor
Posts: 23
Joined: Mon Dec 17, 2018 10:24 pm

Re: Maternal Inheritance

Postby Nikki2019 » Fri Jan 11, 2019 4:56 pm

Hi slacker ,

I was just wondering if others in the forum know about this and if its valid, perhaps from their own research?

I don't have the specific study the book was referring to right now.

NF52
Support Team
Support Team
Posts: 861
Joined: Tue Oct 25, 2016 9:41 am
Location: Eastern U.S.

Re: Maternal Inheritance

Postby NF52 » Fri Jan 11, 2019 6:30 pm

Nikki2019 wrote:Hi slacker ,I was just wondering if others in the forum know about this and if its valid, perhaps from their own research? I don't have the specific study the book was referring to right now.
Hi Nikki,
You are doing lots of reading, across a huge array of topics! We have members who (sort of) jokingly refer to that as "drinking from the fire hose of information". It's a great way to get a sampling of lots of different views, and research interests, as long as you know that much research is by its nature "basic", meaning looking to identify how something happens, not "clinical", meaning ready for use in humans.

Mitochondrial DNA research is in that camp. As Slacker noted, we inherit out mitochondrial DNA from our mothers (with a few weird biological exceptions). But mitochondrial disease is far harder to identify than simply looking for an ApoE 4 gene.
Here's an explanation I found:
Mitochondrial diseases are the result of either inherited or spontaneous mutations in mtDNA or nDNA which lead to altered functions of the proteins or RNA molecules that normally reside in mitochondria. Problems with mitochondrial function, however, may only affect certain tissues as a result of factors occurring during development and growth that we do not yet understand. Even when tissue-specific isoforms of mitochondrial proteins are considered, it is difficult to explain the variable patterns of affected organ systems in the mitochondrial disease syndromes seen clinically.
https://www.umdf.org/what-is-mitochondrial-disease/

Scientists are only beginning to develop the technology to study mitochondria in more than a few areas. So while it's likely that some mutations (or variants, as scientists are sometimes calling these changes) may cause changes that combine with other factors to increase the risk of Alzheimer's disease or other diseases, we are a long way from being able to look at your 23&me profile and see if you have these changes. So I put these kinds of studies in the "interesting, but doesn't change a thing I need to do now" basket.

Here's another article that does a nice job of reviewing the progress to date (and most of it is way beyond me!)
In summary, there is significant evidence for the role of mitochondria in AD risk. Studies of the contribution of mitochondrial genetic variation to AD risk remain inconclusive due to small sample sizes, limited genetic data collection, and inadequate approaches to association analysis. Growing sample sizes and the more widespread use of whole genome sequence data in the study of nuclear genetic risk factors for AD can also be leveraged for the study of mitochondrial genetic variation in AD...and provide a positive outlook for future investigations of mitochondrial genetic contributions to AD risk.
Mitochondria and Alzheimer’s Disease: the Role of Mitochondrial Genetic Variation
4/4 and still an optimist!

Nikki2019
Contributor
Contributor
Posts: 23
Joined: Mon Dec 17, 2018 10:24 pm

Re: Maternal Inheritance

Postby Nikki2019 » Fri Jan 11, 2019 6:43 pm

Thanks NF52 for responding to my inquiry. I think I may be grasping at straws, since in my case, it is my father has AD very young.

Fiver
Senior Contributor
Senior Contributor
Posts: 441
Joined: Wed Feb 01, 2017 12:51 pm

Re: Maternal Inheritance

Postby Fiver » Sun Jan 13, 2019 9:51 am

Hi Nikki2019. You already got good information above. Here's how I think about it.

Mitochondria maintain only a small subset of the genes they had when they were once free-living bacteria. After millions of years of living inside our cells they are passed many of there genes over to the host cells and import the gene products as needed, and allowed by the host cell. Those that remain in the circular mitochondrial genome include the one your mention, and a few others coding for components of the ATP generating system. You're right, we inherit mitochondria (and their genes) from out mothers....except in very rare cases

Harmful mutations in mitochondrial genes often cause problems with ATP production, sometimes resulting in the generation of harmful reactive oxygen species (ROS) - things like peroxides that damage cells. Sometimes levels of ROS protective enzymes are reduced too. This tends to impact our most energy-dependent and sensitive tissues.....usually in the nervous system. There are genes linked to poor energy levels, late-life blindness, and mitochondrial dysfunction, for example.

Some of these could, in theory, harm cognition. But they aren't normally linked directly to Alzheimer's disease, at least they aren't commonly discussed in this way.

One approach researchers take to try and help with the broad range of mitochondrial disorders or those with some indirect link is to stimulate mitochondrial biogenesis. Old mitochondria have more problems. So encouraging our cells to make brand new ones and destroy the old one in some orderly fashion seems to help....well, seems to help mice, including those with mouse versions of Parkinson's, ALS, muscular distrophy, etc. The drugs and substances that seem to encourage mitochondrial biogenesis include things like resveratrol, AICAR, etc. They seem to work through some of the pathways that might have some link to mTOR, sirtuins, cell energy sensing, etc. Exercise can help, apparently. Caloric restriction seems to help, again, mostly in mice as far as my reading goes.

So, if there is a useful link for apoe4s to think about it is probably this:

healthy mitochondria are important, especially to the nervous system
young mitochondria are usually the most healthy
so stimulating "mitochondrial biogenesis" is probably helpful
some of the things discussed here for AD - exercise, supplements, for example - might do this.

So like others have said, this is already built in to most of the lifestyle prevention programs.
Last edited by Fiver on Sun Jan 13, 2019 11:37 am, edited 1 time in total.
Reading studies, need coffee. All I know: it's beautifully terribly complex. It's really a miracle that any of it works at all. Being healthy, but sometimes this mess of billions of neurons has had enough avocados and just wants a crunchy cookie.

NF52
Support Team
Support Team
Posts: 861
Joined: Tue Oct 25, 2016 9:41 am
Location: Eastern U.S.

Re: Maternal Inheritance

Postby NF52 » Sun Jan 13, 2019 10:01 am

Fiver wrote:So, if there is a useful link for apoe4s to think about it is probably this:

healthy mitochondria are important, especially to the nervous system
young mitochondria are usually the most healthy
so stimulating "mitochondrial biogenesis" is probably helpful
some of the things discussed here for AD - exercise, supplements, for example - might do this.

So like others have said, this is already built in to most of the lifestyle prevention programs.

Thanks Fiver, for a MUCH better explanation! When you need science explained, it always helps to ask a scientist! ;)
4/4 and still an optimist!

Fiver
Senior Contributor
Senior Contributor
Posts: 441
Joined: Wed Feb 01, 2017 12:51 pm

Re: Maternal Inheritance

Postby Fiver » Sun Jan 13, 2019 11:39 am

NF52, your description was great! I was recently reading up on this, so I was excited to see this thread. :)
Reading studies, need coffee. All I know: it's beautifully terribly complex. It's really a miracle that any of it works at all. Being healthy, but sometimes this mess of billions of neurons has had enough avocados and just wants a crunchy cookie.

Tincup
Mod
Mod
Posts: 2190
Joined: Fri Aug 08, 2014 2:57 pm
Location: Front Range, CO

Re: Maternal Inheritance

Postby Tincup » Sun Jan 13, 2019 7:56 pm

Nikki2019 wrote:I came across some reading which states that a "mutation in the DNA of the mitochondria of the cytochrome C oxidase gene" means that if mom passed it on you than you are 9 times more likely than if dad did? Do you think this is just based on a small study ?


Doug Wallace is the guy who figured out maternal inheritance of mitochondrial DNA. My understanding - mixing up mitochondrial DNA is bad - as opposed to what we see in nuclear DNA. When mitochondria age, you get more "heteroplasmy" or difference between the DNA. This can degrade the energy production of the mitochondria. What Wallace has observed is you get different illness phenotypes in a step function as hetroplasmy increases. This is a good interview/podcast he did on STEM Talk. This is a presentation he did on his work 3 years ago.

My understanding is that mitochondrial energetics (or the degrading of them) may be upstream of many illnesses, including cognitive decline.
Tincup
E3,E4

Nikki2019
Contributor
Contributor
Posts: 23
Joined: Mon Dec 17, 2018 10:24 pm

Re: Maternal Inheritance

Postby Nikki2019 » Sun Jan 13, 2019 8:15 pm

Thanks, Tincup

So do you think that it may be the case that if dad has AD one is generally less likely to get it than if mom has it?


Return to “Science and Research”

Who is online

Users browsing this forum: No registered users and 2 guests