Common Mutations

 

Mutation drives evolution. Evolution proceeds through mutation.

Fresh out of the COVID pandemic we’ve come to dread our mutations. We test for signs of mutation with fear and loathing. It’s past time we corrected our attitude toward this inevitable and constant process.

The force that steered us from a future as a puddle of amino acids or a bacteria flagelatting around without a nucleus or purpose is mutation.

Everything changes constantly. And the engine of change in biological systems is: Mutation.

A handful of the most common driving and passenger MPN mutations currently discovered create the proteins that play a role in the swelling, itching, inflammation and fatigue that characterize the myeloproflierative chaotic blood production system. (Hematopoiesis.)s.

There are many more mutations than those treated here, some likely more significant, but these, lab tested and verified, may do for a start.

Mutations arise in the course of cellular reproduction, a complex and decidedly unsexy process of spindles and splitting, chromosomes and transcription to messenger RNA .. From there, it;s on to translation to proteins via ribosomes cruising our cytoplasm before getting folded into a workable, functional proteins. Trillions of cells continually reproduce their yards long alphabet soup of DNA with the inevitable errors – changes — arising from copying, moving, shifting, etc.

Mutations occur within genes, clearly defined relatively short sections of DNA. Sometime they take off expand, usually not. And unless the mutation occurs within the germline – egg and sperm cells –they are somatic and not passed along to our kids.

Our genome is made up of two long strips of DNA, one from Mom, one from Dad. If a mutation occurs in a gene on one strip only it’s homozygous. If it occurs on both strips its’ heterozygous.

Which gets us to allele burden. The percentage of a mutated gene in our genome is the allele burden. So if you’re homozygous for a mutation your maximum allele burden is 50%. Heterozygous? 100%. Unmutated genes are called WT or Wild Type.

Good news: Some mutations are good for us, help assure our survival. Most mutations, which occur in single cells don’t last very long or are otherwise of little significance. But the bad news is a few are downright nasty and if they include a survival advantage, they can increase in number and power and create problems.

The type of mutation — Good, Bad, Neutral — can be further characterized by function: Some mutations affect signaling, some assisst in turning a gene on or off, some drive the development of MPN, some are just along for the ride. The impact of a particular mutation depends on where along the sprink;ing of Letters (bases) the mutation has occurred. All ASLX-1 mutations are not equal.

Some letters help code for success, some for failurea. The Letters — bases  or nucleobases –A=are Adenine (A), Guanine (G) Thymine (T) Cytosine (C) and Uracil (U))  These compounds are the nitrogen containing molecules that are at the hearet of tthe twisted double helix DNA or RNA ladder . (G) is always paired with (C) and (A) is paired with (U) or (T).

 

The most common MPN mutations
Rank and Type

                              Mutations Rank.                TYPE

Here’s an alphabetic listing of t5 common mutations found in MPN patients with expanded information.

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