Understanding: What The Heck Is A 'Genetic Disease'?

in #steemstem6 years ago (edited)

Today we are going to take a break from breaking down primary literature publications to discuss a topic that you likely see thrown around in the news semi regularly these days. Genetic Diseases. Now more so then ever at any point in history we are all regularly exposed to a LOT of complex science (you may not even realize it), especially if you keep up with news about modern advancements in health treatments. In reading articles you will hear about things like: 'precision medicine', 'genomic screening', 'genetic diseases.' Lots of fancy sounding terms, that some of you may not even know what mean (but hey the scientists talk about them, so it must be very technical and only they could possibly understand it, right? Wrong!).

Why don't you take a brief moment out of your day, and join me in expanding your understanding of science just a little bit? The more you know about some basic concepts, the better you can understand treatments that you may be receiving at some point in the future!


Now, to answer the above question of what is a Genetic Disease we must cover a few basic topics, including: what is a protein/enzyme and how does one get built? What is a mutation and what does that mean for a protein? And finally, an example of a genetic disease. So lets get started, I promise this won't take too long (... maybe it will ;) depends on how closely you read) and think you will come out knowing/understanding more then when you went in.

What is a Protein/Enzyme and How Does One Get Built?

Proteins, you know protein is important, you are supposed to eat a bunch of it right? However what even is it? Protein is actually not an it, but rather many different things, and they are not just some abstract part of food.

Side Note: For most people a major source of protein in food is derived from meat aka muscle which is mostly composed of two major proteins called actin and myosin.

Second Side Note: When you eat food for 'protein' your body actually isn' interested in the protein itself, but rather in breaking it down for the amino acids which it is made up of... but more on that later

In fact there are many many varieties, in your body there are more than two million, completely unique types! Which to many of you might be surprising, but maybe less so when we think about what proteins actually are.

Proteins are largely two things to our bodies, they are the material that the structures in our cells are made up of (so they are structural proteins, or Scaffolds) and they are also molecular machines which allow very specific chemical reactions to occur (the molecular machine type proteins are called Enzymes, and they are the focus of my career).

All of the 20 major amino acid R-groups separated by their individual chemical properties

Now these protein machines and scaffolds are actually made up of building blocks called amino acids. Each amino acid is unique from the next only in one section (called a substituent side chain or R-group), these R-groups are what give the amino acid its properties, be that a positive or negative charge, attraction to water (hydrophillic), or a strong dislike of water (hydrophobic). When proteins are being built in/by a cellular structure called the ribosome Amino acids are assembled together into a long chain called a polypeptide.


Simulation of protein folding

Now those amino acids all have unique chemical properties, some of them are attracted to each other, others are repelled by each other, some like water and want to be in contact with it, others hate it and want to be away from it. These properties result in the peptide chain that gets assembled folding up on itself, and it keeps folding, and folding until it is a giant blob where all of those chemical properties are in a state where they are happiest (lowest energy). We call this folded state a protein.

Some proteins (Enzymes) have particular spots where the chemical aspects of the amino acids allow for chemical reactions to occur, these spots are called active sites.

Taking A Step Back Into The Ribosome

These are the 'codon' codes, which tell the ribosome what amino acid to add next in the polypeptide chain

Now we know how a protein is put together a little bit, but for the next section (mutation) we must first talk about how the amino acids are selected (briefly). This is determined based on the instructions provided to the ribosome on a piece of RNA which itself gets transcribed from a gene located in our DNA. These RNA transcripts are organized into 3 nucleotide (the building blocks of DNA/RNA) groupings called codons. The order of the nucleotides (the A, T, C and Gs of our genetic code) in each codon, tell the ribosome specifically what amino acid to incorporate next.

So, we've established what a protein is, how it is built, and where the instructions come from, which is all find and good when things are working as intended... but what about when things break?

What Is A Mutation And What Does It Mean For A Protein?

A mutation is just a change to the sequence of your genetic material. There are a ton of reasons WHY a mutation can occur and for the purpose of this blog the why isn't important. We are just concerned with the what. Say we have a DNA sequence AATTAAGGC, a mutation would be a change to ANY of those nucleotides in the sequence, if something happened and the sequence became AATGAAGGC then that is a mutation because a T became a G.

Now this potentially has a downstream effect on EVERYTHING, remember above we talked about how the ribosome assembles proteins based on codons right? And that those codons correspond to specific amino acids? Well say a mutation happened inside of a codon... one that was supposed to be telling the ribosome to put a Alanine, next into a polypeptide chain... that codon sequence is say... GAA, but a mutation happened and changed that G to a A so now the codon reads AAA well the ribosome will read that and incorporate the appropriate amino acid, which is now a Lysine.

THIS can cause a HUGE change in how an enzyme functions, because we have converted the chemical properties of the amino acid in a particular location in that protein. We went from an alanine which is hydrophobic (somewhat) and has no charge, to a lysine which is big and positively charged. Thats a big difference we changed everything about the properties.

Now say that alanine was located in the active site of an enyzme, it was sitting where a very specific chemical reaction was happening, one which required precisely the conditions which that enzyme allowed for. However, NOW we have altered the conditions and put some extra positive charge there. The chemistry may not work the same way now, the conditions are ruined (or maybe it works slower... or maybe it actually works much better! either way it is changed).

This is what happens in a Genetic Disease, a mutation happens in a particular spot in a gene, which results a change in how the protein functions, because the protein has a building block change. Its like taking a piece out of a finely tuned machine (say your computer), putting in a different one, and still expecting that machine to run the same way. Maybe it was replaced with something else. Okay if you replace your CPU with a faster one, it will still run, but if you replace your CPU with a capacitor... well that's not going to work out too well for the machine's computation abilities.

Example Of A Genetic Disease

The Wheel of Diseases!!!

Lets end with an example of a genetic disease. I will spin the wheel of diseases.... and its landed on Haemochromatosis. Haemochromatosis is a genetic disease which results in drastically increased absorption of iron from our diets. This disease is believed to be caused by one of two mutations which happen in the gene for a protein called the human haemochromatosis protein (WOW... so creative in the naming...) or HFE. The mutations that happen either change one cysteine, the 238th amino acid in this proteins polypeptide chain, to a tyrosine, or change of a histidine, the 63rd amino acid in the proteins polypeptide chain, to an aspartate.

These mutations to the gene cause a protein to be made which just isn't able to regulate the amount of iron which gets absorbed by the body. Unlike with other ions, our bodies don't have a good mechanism to get rid of excess iron either. So it leads to accumulation in all sorts of location.. most severely in the liver leading to cirrhosis or cancer. However the damage is not limited to there, as multiple organ systems are effected by this accumulation of iron. Currently treatment is limited to blood letting, or chelation therapy where compounds are given that trap the iron and allow it to be excreted from the body by the kidneys.

Conclusion

I hope this post has helped paint a better picture in your mind of just what a genetic disease is, and I hope the information will prove useful in helping you better understand all of the future medical treatments that are in store for us all as research and technology continue to progress. I have tried, throughout this post to provide you with a variety of links and other simple sources with which you can use to further your knowledge on the individual topics we discussed throughout. I have made heavy use of wikipedia sources as I find it to be relatively easy to digest as one attempts to gain an understanding of the basics of various topics.


Sources

Image Sources

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Gif 1
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Text Sources

  1. https://ghr.nlm.nih.gov/primer/precisionmedicine/definition
  2. https://www.sciencedaily.com/releases/2013/03/130307124552.htm
  3. https://www.genome.gov/10001204/specific-genetic-disorders/
  4. https://en.wikipedia.org/wiki/Actin
  5. https://en.wikipedia.org/wiki/Myosin
  6. http://www.innovateus.net/health/how-many-proteins-exist-human-body
  7. https://en.wikipedia.org/wiki/Scaffold_protein
  8. https://en.wikipedia.org/wiki/Enzyme
  9. https://en.wikipedia.org/wiki/Substituent
  10. https://en.wikipedia.org/wiki/Hydrophile
  11. https://en.wikipedia.org/wiki/Hydrophobe
  12. https://en.wikipedia.org/wiki/Ribosome
  13. https://en.wikipedia.org/wiki/Peptide
  14. https://en.wikipedia.org/wiki/Protein_folding
  15. https://en.wikipedia.org/wiki/Active_site
  16. https://ghr.nlm.nih.gov/primer/basics/gene
  17. https://en.wikipedia.org/wiki/Nucleotide
  18. https://en.wikipedia.org/wiki/DNA_codon_table
  19. https://en.wikipedia.org/wiki/Mutation
  20. https://en.wikipedia.org/wiki/Alanine
  21. https://en.wikipedia.org/wiki/Lysine
  22. https://en.wikipedia.org/wiki/Capacitor
  23. https://en.wikipedia.org/wiki/HFE_hereditary_haemochromatosis
  24. https://en.wikipedia.org/wiki/HFE_(gene)
  25. https://en.wikipedia.org/wiki/Cysteine
  26. https://en.wikipedia.org/wiki/Tyrosine
  27. https://en.wikipedia.org/wiki/Histidine
  28. https://en.wikipedia.org/wiki/Aspartic_acid

SteemSTEM

If you haven't heard about the SteemSTEM project yet (WHAT do you live under a rock!? Just kidding), and are reading this post then I highly recommend you take a look into it! The SteemSTEM team has been working for over one year now to promote promote well written/informative Science Technology Engineering and Mathematics postings on Steemit. The project (@steemstem) seeks to build a community of science and technology lovers on steemit and ade in nurturing the growth of blogs that will make steemit a go-to source for science/tech information, news, and just generally fascinating content.

To learn more about the project please join us on steemit.chat (https://steemit.chat/channel/steemSTEM) or on discord, we are always looking for people who want to help in our quest to increase the quality of STEM (and health) posts on our rapidly growing platform!

Finally thanks to @rocking-dave for the great gif set that so many members of the community use in their posts. They look fantastic.

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Nice explanation of the basics. Interesting side note about hemochromatosis. A football fan with the disease went undetected for years because he constantly donated blood to afford tickets. He might have even been saved by his constant donating.

http://abcnews.go.com/Health/MensHealth/football-fan-paying-tickets-saved-fatal-disease/story?id=10109129

Well this is a fun story.

Thumbs up from the molecular biologist for this one! My biggest struggle has always been to explain these stuff in simple and understandable way to people who do not have formal education in biology/biochemistry/etc., but you obviously do not have that problem :)

It takes some practice, have you ever taught undergraduates? Like freshmen? I generally try to talk about things how I would during say office hours with a freshman science student. Try to make it relate-able at least a little bit, while still maintaining the core facts.

interesting, I think I had it all backwards concerning proteins.

Well, then you really got something out of this post then :)

That is awesomely explained, the first thing that comes to mind whenever I hear about a genetic disease is that disease someone gets due to the family where one happened to be born in. Thank you for breaking down a very confusing subject in clear, simple terms devoid of jargons that scare people.

Thanks for reading!

This is the first time I'm seeing protein explained this way. It is almost as if I did not pay any attention to the biology class. DNA sequencing looks like a pretty tough test to do. Thank you too.

Great information and thank you. My brother was in great health, or so he told us, until one day he was at the doctor's office for a routine checkup and had to be rushed to the hospital. They found all kinds of problems from fluid around his heart to a lung infection. From then on he was in and out of the hospital until about 2 years later he lost his health battle. I appreciate learning and am able to understand more from your in depth posts.

This is a scary story! I am sorry to hear about your brother.

It's written beautifully and well explain, even to people without any knowledge in the matter.
I have never heard of steemSTEM before, sounds like a great project, hope to join in quickly! (couldn't join the discord channel, does the link work?)
I study Bioinformatics and has a lot to put in :-)

Thanks! Yeah, steemSTEM has been around for just about 1.5 years, growing pretty rapidly these days :D

couldn't join the discord channel, does the link work?

Crap, I forgot to click to make a link that doesn't expire! I have fixed it!

I have family in medicine and research. My cousin has recently started her own practice and i hope to share this type of work happening here on steemit. It's a thriving community with a diversity of interests. Speaking for myself, these sorts of posts are appreciated because I teach improv. We have many students who attend the nearby Washington University and practice medicine at Barnes Jewish and Cardinal Glennon. They make for fun players and I'm always encouraging them to bring their refernce level of expertise to scenes. This sort of thing helps me relate to them to let them know improv is not just jokes, but one can do scenes about fascinating specific topics such as what the heck a genetic disease is anyway. :)

I am 'almost good' at having a perfect understanding of molecular biology until when it gets to mutation. I slept off in the class while the Prof. was explaining it...lol. You did justice to that man.

As a microbiologist, I really think Several types of muta­tions exist. Some arise from the alteration of single pairs of nu­cleotides and from the addition or deletion of one nucleotide
pair in the coding regions of a gene.

Yes, Indels are a thing, so is oxidative damage, and formation of a variety of nucleotide adducts... However that level of detail was not necessary given the intended audience of this post (non scientists).

Oh. I understand now. It is made for the whole entire steemit community. Sorry for any unintended shade.

Thank you for the time and effort putting this together👍
Great information
And put together very well!

I can’t lie
Much of this was over my head but I found it interesting nonetheless

Thank you for addressing the issue of health with certainty as the progress of medical science Some genetic and also non-genetic diseases occur as a result of a change in DNA composition, whether it is a decrease, increase or replacement of one of the nucleic acids by another, and this is called a mutation. To do gene analysis, doctors look for this mutation "to mean any change in the composition of the nucleic acid" or otherwise or otherwise make sure the sequence of DNA is healthy and does not increase or decrease or alter.
upvoted and resteem @aherbil

Yep, for genetic diseases, doctors will sequence your DNA to determine what errors have occurred that cause the symptoms.

Yes @justtryme90
Gene and DNA testing is usually done in three steps:

  1. Taking a blood sample or other tissue from the body and separating the genetic material from it.
    2 - Reading DNA sequences with special tests may sometimes be complicated.
    3 - Comparison of the result of this examination with a healthy copy of the gene studied, and due to some complications in reading the DNA sequence due to the size of the gene to be examined or other things, the laboratory may examine a specific part or parts of the gene to make sure that it is sound and choose these other parts based on previous research Indicates that this segment is abundant in mutations compared to other parts. Therefore, it should be noted that the examination of the gene does not necessarily examine all genetic matters of the disease, but may be analysis is a partial analysis and not a complete analysis.

Just imagine the near(?) future once the genetic alphabet is extended with some xeno...

From time to time I visit this group to see what's new.

Sorry for a partial off-topic, but I guessed this would be interesting to you.

I will join you and I try to follow you because your health knowledge is shared with others. from this analysis I know about health in one community. thanks for your analysis. good work @justtyme90

the post is great and awesome

Thank you :)

Wonderful to see effective science communication on Steemit! Thank you for your contributions :)

Thanks for the kind words!

good job. I will follow your post next thank you very much @justtryme90

Thanks for breaking down something like 'peptide chain' down into something more understandable for lay persons such as myself. Thank you

Thanks for reading, glad you got something out of the post. :)

I really did. Thank you.

Now those amino acids all have unique chemical properties, some of them are attracted to each other, others are repelled by each other,

This reminds me of the concept of bonding, in which molecules are formed based on their attraction, either ionic, covalent or others.

some like water and want to be in contact with it, others hate it and want to be away from it.
I would be correct to say their chemical composition makes up for this. Hydrogen bonding promotes hydrophilic(water likeness).

These properties result in the peptide chain that gets assembled folding up on itself, and it keeps folding, and folding until it is a giant blob where all of those chemical properties are in a state where they are happiest (lowest energy).

This gives me a full grasp of the understanding of the complex and polymer nature of proteins. Since all molecules want to achieve a state of minimum energy.

Thank you for this post. It was an easy read.

This reminds me of the concept of bonding, in which molecules are formed based on their attraction, either ionic, covalent or others.

Well it is, its all about the chemistry :)

Glad you liked the post turpsy.

Really helpful and long post . As a medical person i know about it But i read your post , It was great keep it up man , @justtryme90

Wow ..great article. A side note: just because "it's genetic" doesn't mean we are doomed to experience it. From what I have seen, many genetic illnesses won't manifest symptoms if certain nutritional needs are met and toxins avoided. For example, diabetes runs in my best friend's family. His mother, her sister, his brother, grandfather ....uncle -- they ALL have diabetes and they ALL are on the "Standard American Diet". My friend on the other hand is on the raw ketogenic diet and is able to live a healthy, normal life free of insulin injections simply by addressing his particular genetic condition with diet ...while the relatives are constantly going to the doctor -- one might lose his foot. Another is going blind.

just because "it's genetic" doesn't mean we are doomed to experience it.

It depends on the disease. In certain cases, if you have the mutations you WILL be experiencing it, and in the cases of these diseases its very often from birth.

I have a little question to ask sir:
Can diseases caused by genetic transmutation be inherited by subsequent generations, even with the dominating effect of natural selection?
This is a very expository piece sir.

Can diseases caused by genetic transmutation be inherited by subsequent generations

Yes so long as the mutation is carried in the germ line.

Thanks for the kind response sir

I have translated to Turkish and read a very successful article

Thanks! Glad the material still comes through after translation!

good post

This is a really mind blowing write up, i need to start using as guide to make mine.

Thanks, glad you got something out of it :)

awesome post

informative post kindly if you can answer my quick question is diabetes is a genetic disease

It can be yes, but is not necessarily.

thanks for answering my grandmother and now my mother they both have diabetes.

Thanks for the important info
@resteem

Wow, nice post! I learn a lot about this subject in my biology courses, but this article gave me more informations about the subject so thank you @justtryme90 I appreciate.

Olivia D.

Thanks Olivia!

Btw, if you have some interest on green energy and their economic advantage I have done two articles who talk about this subject! Maybe you can take a look and give my advices and your opinion! Good day.

Olivia D.

A well explained post about genetic disease.

But I must say with all the terms you introduced me to am more than confused.

But this has also given me the desire to know more. Thank you for the links and sources. I will check them out for better and further understanding

But I must say with all the terms you introduced me to am more than confused.

Yep this is why I provided lots of links!

This post is very enlightening, but please permit me to ask.

People with genetic diseases like Haemocromatosis, what kind of treatment can be recommended for them

I described it in the text of the post.

thank you for the information .. a very good job deserve a great reward ..

very good, happy work i will follow your next post
@justtryme90

Thank you very much :)

I was making fun of @mobbs face yesterday. You posting this today can't be a coincidence...

Mobbs's face is a genetic disease?

No, just a symptom you dummy!

Ahhhh I see

thank you @ justtryme90 incredible information what you write will be very useful for me and friends steemit who read it, continue to share

A very details post on genetic, starting from very basics. Some people might find it difficult initially, but nothing can be simpler than this.

Thanks, i think its really important these days to have a little bit of an understanding of this stuff. Its honestly so very prevalent in modern society, and often times decisions we are forced to make truly NEED a bit of knowledge in order to make the best possible choices.

Yes. With the improvement of modern science as well as medical fields, the incidence and prevalence of genetic disease is increasing. Environmental factors, added chemicals in food etc have contribution in it too. So general population should also have some idea about it.

wow! just mindblowing post with nice article.

Hi dear i notice that you didn't post since 6 days hope everthing is going alright with you and hope post something new again im waiting your useful posts

I am really busy with steemSTEM, I work on stuff for a while and eventually get a post out. All is well, you can expect a post from me once per week or so :)

got to know things

I'm glad you got something out of it

There are about 17,000 different proteins known in your body and we think there are a few thousand more, but they could be modifications. 2 million different proteins gives a bad picture, this is only the upper theoretical limit for how many different proteins our DNA COULD code for. It would never work if they were expressed!

https://www.proteinatlas.org/

Thanks for good reading :)

2 million different proteins gives a bad picture, this is only the upper theoretical limit for how many different proteins our DNA COULD code for.

No, it creates the thought I was going for, that there are a massive variety of different proteins all with unique function. Beyond this we have about 17000 protein coding genes (that we know of), however splice variants alone I dictate the varieties of protein to be in the 100,000s so I don't feel the theoretical limit is all that misleading.

In fact there are many many varieties, in your body there are more than two million, completely unique types!

There are 17,000 proteins and possibly a few thousands more, PTS and splice variants change nothing of what you stated since they are not uniqe types.

Just making it clear!

thanks!

PTS and splice variants change nothing of what you stated since they are not unique types.

They are unique types. Enzymatic function (in the case of an enzyme...) will likely not change but cellular localization, or complex binding function can drastically differ. A protein +/- it's NLS is a very different thing, despite the similar enzyme function.

I disagree with your suggested correction.

Yeah you are free to define unique types as u like! I merely clarify how many different proteins is expressed in our body according to classic biochemical definition, iso-forms and PTS mods are defined as the same protein, as for splicing goes the same thing as long as conformation is preserved, affinity for different binding sites etc change no classifications :)

Thanks for answering

I like your context and there are no contradictions :) just saw it as a bit unclear when it came to the number of unique proteins and now anyone who wonders can check!

https://en.wikipedia.org/wiki/Protein_isoform

AMPK have different subunits in different cells.
In human skeletal muscle, the preferred form is α2β2γ1, But in the human liver, the most abundant form is α1β2γ1.
So even when subunit composition and thereby massive conformational differences is seen, its still the same protein :)

I would even state that most alternatively spliced expressions result in common iso-forms with the same function!

i´ve done exon skipping in drosophila resulting in 3 identical structures and the rest unexpressed :)

Okay if you replace your CPU with a faster one, it will still run, but if you replace your CPU with a capacitor... well that's not going to work out too well for the machine's computation abilities.

Nice way to illustrate missense and nonsense mutations. Gonna keep it in mind for a future post! Will not credit you.
:p

Interesting thing, mutations, it's the enabler of evolution, but most of the time it's harmful. If everything copied itself perfectly we would remain stagnant and die off as soon as the environment changed. Diseases is the price we pay for adaptability, in a way.

I just always thought this is fascinating...

but most of the time it's harmful

Well much of the time it's silent. Silent mutations occur all of the time, masked by the repeated codons corresponding to the same trans.

thank you for sharing information may be useful for us all, Success for you, Success for you, Success for you @justtryme90

great post
thanks for this information

Hey, nice write, it is interesting. I am following you, can you follow me @xtophercruzeu thanks

It's original work.

It is, thanks.

You got a 4.40% upvote from @postpromoter courtesy of @justtryme90!

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