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Are All Genetic Conditions Hereditary?

Whenever we hear the word genetic, the first thing that comes to mind is that the whole family would be affected or that it would definitely be passed down. This can create confusion or mayhem. But in reality, this is not true in most cases. The terms mutation and genetic variant are often used interchangeably. In this article, we mostly use variant, while some of the visuals may refer to mutation, they mean the same thing in this context.


What Are Genetic Variants?

Genetic changes (mutations or genetic variants) can affect anything from a single-letter change (DNA chemical letters - A, T, G, and C) to large chunks of DNA encompassing multiple genes (many letter sequences). Not all genetic changes are harmful or detrimental to health. Some of them are natural variations, which is why we are all different in our own ways (in terms of how we look and function).


Classification of Genetic Variants

Genetic variants can be classified in two major ways:


Acquired (or Somatic) Variants

The word somatic comes from the Greek word soma, which means “body,” and can be further defined as the parts of an organism other than the reproductive cells (sperm and eggs).

Somatic variants occur at some point during a person’s life and are present only in certain cells, not in every cell in the body. These changes can be caused by:

  • Environmental factors such as UV rays from the sun

  • Errors during cell division as DNA makes copies of itself

Somatic variants in somatic cells (all cells of the body other than sperm and egg cells) cannot be passed on to the next generation.


Hereditary (or Germline) Variants

These are inherited from a parent and are present throughout a person’s life in almost every cell in the body. These variants are also called germline variants because they are present in the parents’ egg or sperm cells, which are also called germ cells.

When an egg and a sperm cell unite, the resulting zygote (the fertilized cell when the sperm and egg unite) receives DNA from both parents. If this DNA has a variant, the child that grows from the zygote will have the variant in each of their cells.


Differentiation between a acquired (somatic) and hereditary (germline) variants (also called mutations)
Differentiation between a acquired (somatic) and hereditary (germline) variants (also called mutations)

Example: Cancer as a Genetic but Not Always Hereditary Condition

For instance, cancer is a genetic condition. When variants in the DNA disrupt its protective functions, this leads to uncontrolled growth of cells, resulting in cancer.

Only 5-10% of cancers are hereditary, meaning they can be passed down from one generation to another. However, most cancers are caused by somatic variants, which can be detected in the tumor site but not in other parts of the body, indicating that it is unlikely to be passed down.

Therefore, we understand that not all genetic conditions are hereditary (they can occur because of somatic variants), but all hereditary conditions are genetic.


Special Cases of Genetic Change: De Novo Mutations and Mosaicism


De Novo Variants

Some genetic variants can be de novo (derived from Latin meaning “anew”) variants, and these can be either hereditary or somatic.

  • In some cases, the de novo variant occurs in a person’s germ cells but is not present in any of the person’s other cells. In such a case, the person can pass it down to their offspring.

  • In other cases, the de novo variant occurs in the zygote, shortly after the egg and sperm cells unite. As the zygote divides, each resulting cell in the growing embryo will have the variant.

It is often impossible to tell exactly when a de novo variant happened. It could have occurred during the formation of germ cells or during conception and development.

For instance, if a genetic condition is present in one family member (variant present in all cells of their body), but not in either parent, and there is no family history, this could indicate a de novo variant, either present only in the parent’s germ cells or arising during the earliest stages of conception or development.


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Mosaicism

Somatic variants that happen in a single cell early in embryonic development can lead to a situation called mosaicism. These genetic changes are not present in a parent’s germ cells or in the zygote, but occur slightly later, when the embryo includes several cells. (Embryo: early stage of development starting from the zygote and lasting until the eighth week of pregnancy or tenth week after the last menstrual period, before transitioning into a fetus.)

As all the cells divide during growth and development, cells that arise from the one altered cell will carry the variant, while others will not. Depending on the variant and how many cells are affected, mosaicism may or may not cause health problems.


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References: 

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