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DNA Inheritance
We all know that we share something with the people we are related to. This is because we inherit DNA from our parents, who inherited their DNA from their parents. Our DNA is packaged into 23 different chromosomes. We have two copies of each of these chromosomes, one set that we get from our mother and the other set we get from our father. That gives us a total of 46 chromosomes arranged into 23 chromosome pairs. When we inherit those chromosomes from our parents, we also inherit the DNA sequence variants, which is why people tend to look more like their parents and siblings than other people.

Precision Medicine Today There are different ways that traits and diseases can be passed through a family. Some traits and genetic diseases are influenced by only one gene, whereas others are influenced by multiple genes. For some genes, a single variant can dramatically influence your risk of getting a certain disease. The majority of these diseases are rare and the chance that you will get the disease depends on how that variant is inherited. Some examples of rare single-gene diseases include cystic fibrosis and Huntington’s disease. Other diseases are caused by variants in many different genes in your genome. The risk that someone develops type 2 diabetes, for example, is determined by the combination of variants in more than 8 different genes.

There are two basic modes of genetic inheritance that describe how single-gene diseases are passed through a family: dominant and recessive. Recessive diseases, like cystic fibrosis, require two disease-causing variants to get the disease. One variant must be inherited from the mother and the other from the father, even if neither the mother nor father has the disease. For recessive diseases, parents who harbor a disease-causing variant but do not actually show the disease are called carriers. In order for a child to inherit a recessive disease, both parents must be carriers of a disease-causing variant. If both parents are carriers, the chance that they will both pass down their disease-causing variant to a child is 25%.

A disease that is dominant is often seen in every generation of a family. It is passed on directly from a parent with the condition to their child. An example of a dominant genetic disease is Lynch syndrome. Lynch syndrome is an inherited condition which increases your risk for developing many different types of cancer, including colorectal cancer. For a dominant disease, like Lynch syndrome, only one copy of the disease-causing variant inherited from the mother or the father is needed for someone to get Lynch syndrome. The chance that a child will inherit a dominant disease-causing variant from a parent with the dominant disease is 50%.

Occasionally, a person who inherits a single copy of a dominant disease-causing variant from one parent or another person who inherits a disease-causing variant from both parents will never get that disease. For example, a person who inherits a Lynch syndrome variant will not necessarily get cancer. Even though they have the necessary disease-causing variant, it does not mean that they have a 100% chance of developing colorectal cancer. A person who inherits a Lynch syndrome variant has an increased risk, up to 70%, for developing colorectal cancer over their lifetime. This phenomenon is called penetrance. Incomplete penetrance means that not every person with a disease-causing variant will actually get the disease.

Many inherited traits and diseases are more complex, with multiple variants in multiple genes contributing to a disease. Skin pigmentation, eye color, hair color, risk of type 2 diabetes, and many forms of cancer all follow this complex inheritance pattern. These more complex traits do not necessarily follow the typical dominant or recessive inheritance patterns observed in the classic genetic diseases. Instead, the chance that someone has red hair or their risk of developing type 2 diabetes in their lifetime is determined by the combination of variants from many locations in the genome. Complex diseases caused by variants in multiple genes are often strongly influenced by environmental factors. Your risk of developing type 2 diabetes, for example, can only be partially determined by your genetics. What you eat, how much you exercise, and whether or not you smoke also strongly influence whether or not you get type 2 diabetes.

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