Genetic Load, Deleterious Genes, Gene Therapy

Genetic Load

We are all mutants

We all know things about ourselves that we would like to change. But if we only knew more about our genes — good and bad — we would probably know a lot more things about ourselves we would want to change.

An average human newborn contains about 100 new mutations. Most of them will have neutral effect and of the rest, most will have a small deleterious effect.

Genetic Load Definition:

noun The relative difference between the theoretically most fit genotype within a population and the average genotype.

noun The aggregate of deleterious genes that are carried, mostly hidden, in the genomes of a population and may be transmitted to descendants.
Source

As a particular genetic line continues, it accumulates mutations — mostly with a neutral effect on fitness, but not all. Each person’s genome is thus uniquely good and bad.

Deleterious Genes

Deleterious genes tend to accumulate over time unless they are weeded out by natural selection. Some genes are more deleterious than others. Some “bad” genes will kill a child before one year of age, others will allow a person to live several decades — but in an impaired state.

Here is one definition of “a deleterious gene:”

A deleterious gene is one that virtually all reasonable individuals “would judge consistently to cause very premature death or serious health problems that drastically compromise the capacity” of afflicted individuals to carry out normal or near-normal life plans. __ https://sciencing.com/deleterious-genes-14053.html

Of course there are many truly deleterious genes which may not be harmful enough to exactly fit the definition above. The more we learn about the subtleties of polygenic inheritance and interaction, the clearer our concept of deleterious genes (and deleterious gene regulation) will grow.

Gene Therapy

Modern medicine has allowed a lot of people to survive and breed who would otherwise have died off. As a result of modern medicine, the pruning effect of natural selection on deleterious genes has not functioned as previously. This allows more deleterious genes to accumulate, and more genetic load to accrue.

Gene therapy may provide an antidote to some of these unintentional harms brought on by modern medicine.

What is gene therapy?

Gene therapy is an experimental technique that uses genes to treat or prevent disease. In the future, this technique may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using drugs or surgery. Researchers are testing several approaches to gene therapy, including:

Replacing a mutated gene that causes disease with a healthy copy of the gene.

Inactivating, or “knocking out,” a mutated gene that is functioning improperly.

Introducing a new gene into the body to help fight a disease.

__ Source

Two obvious targets for future gene therapy include “genes of senescence” and “genes of senility.”

The use of gene therapy to turn back the clock on ageing is becoming a real prospect.

Exciting new ways of “editing the genome” are hitting modern labs. Scientists are learning to be more precise and effective in targeting specific genes in specific tissues. The technique known as prime editing in principle could correct up to 89% of known genetic variants associated with human diseases. More on prime editing

In a recent gene therapy study in mice published in PNAS, the authors observed:

“We observed a 58% increase in heart function in ascending aortic constriction ensuing heart failure, a 38% reduction in α-smooth muscle actin (αSMA) expression, a 75% reduction in renal medullary atrophy in mice subjected to unilateral ureteral obstruction, and a complete reversal of obesity and diabetes phenotypes in mice fed a constant high-fat diet,” the article’s authors wrote. “Crucially, we discovered that a single formulation combining two separate therapies into one was able to treat all four diseases.” __ quoted here

These effects reversed a number of ageing-related phenotypes in the mice. It is the intent of these scientists to learn how to combine multiple gene therapies into one treatment. They hope to be able to successfully treat both ageing and senility eventually, and are proceeding to studies in dogs.

Summary

We owe our existence to our genes, good and bad. Modern methods of medicine are unintentionally allowing more bad genes to accumulate, but we are learning how to counter these bad genes with more advanced forms of gene therapy. It is a race of mind against biology, with the human mind getting significant help from advanced computing technologies. Example

It goes without saying that if we can use gene therapy to mitigate and reverse the effects of ageing and disease, we might also use gene therapy to achieve “a better normal.” The possibility of raising the average levels of gene expression underlying health, intelligence, creativity, potential for the enjoyment of life, and many other aspects of human existence will be considered by many humans as time goes by. We should pay attention.

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2 Responses to Genetic Load, Deleterious Genes, Gene Therapy

  1. bob sykes says:

    While there is a great deal of promise in gene therapy, costs are being ignored. A relatively simple in vitro fertilization costs about $10,000 per attempt. Much of this is liability insurance. The risk of gene editing by CRSPR or some other technology is that other mutations will be inserted into the genome. The liability associated with that will be astronomic, and the procedure might cost $100,000 or more.

    Gene editing will likely be limited to rich people whose families have known histories of genetic defects. One think of Tay-Sachs disease. The super rich are likely proud of their genes, and seem to prefer natural processes, so they might not participate even if they could afford it.

  2. Once you make “fitness” something other than a reference to “survival,” you’ve solved the circularity problem. But at the cost of using a concept that cannot be observed. These are depths to which biology as a “science” fallen. Leaving us with Chinese Mengeles creating CSPR abominations

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