What are genes and why are they important?

Deoxyribonucleic acid (DNA) is made up of a combination of A, T, G, C basepairs, which code for the various genes in our body. There are over 20,000 genes in the human body, through the proteins they encode, they are the blueprint for how the body functions. Changes or mutations in the DNA may alter the protein product, which can lead to disease. The most common gene mutation involves a change or “misspelling” of the DNA code. Other mutations include the loss (deletion) or gain (duplication or insertion) of a single or multiple base(s). The altered protein product may still retain some normal function, but at a reduced capacity. In other cases, the protein may be totally disabled by the mutation or gain an entirely new, but damaging, function.

Inheritance Patterns

We have 46 chromosomes that come in pairs (23 pairs). One of each pair is inherited from you mother and the other from your father. The last set of chromosomes are called sex chromosomes and are paired as XX (female) or XY(male). There are five basic modes of inheritance for single-gene diseases to exist: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial.

Autosomal Dominant: Only one copy of a gene has a mutation/change in each cell that leads to a genetic condition. There is a 50% risk to pass on the condition to your children and typically each affected person has one affected parent.

Autosomal Recessive: Both copies of a gene has a mutation/change for an individual to be affected with the genetic condition. Parents are usually unaffected but each “carry” a mutation in one of their two copies of the gene. If both parents are carriers of the same genetic condition, there is a 1 in 4 or 25% chance to have an affected child.

X-linked Recessive: A mutation/change is located on the X chromosome. Typically, only males are affected if they have the mutation since they have only one x-chromosome. Females with the mutation are typically unaffected because they have two x-chromosomes, but are considered “carriers”. If a woman is a carrier for an X-linked condition, there is a 50% chance to her son to be affected, and a 50% chance for her daughters to be carriers. If a male is affected then ALL his daughters will be carriers and ALL of his sons will be healthy and not carriers.

Rarely, females can inherit an X-linked recessive disorder. If both parents are affected, ALL of their children will be affected. If the father is affected and the mother is a carrier, 50% of their children will be affected (boys or girls), while the other 50% will be healthy boys or carrier girls.

X-linked Dominant: Similar to X-linked recessive, a mutation/change is located on the X chromosome. However, with X-linked dominant mutations, you only need one mutation to be affected. Both males and females can be affected, although males may be more severely affected or may not survive. When a female is affected, each pregnancy will have a 50% chance for offspring to inherit the disease allele. When a male is affected, all his daughters will be affected, but none of his sons will be affected.

Mutations

Genes are pieces of DNA that instruct our bodies on how to grow and develop. We all have millions of genetic changes; many are benign and do not cause disease or impact our health. However, some changes in genes may be harmful and may cause disease in an individual or when passed down to his or her children. These harmful changes are called mutations or “pathogenic variants” and prevent the gene from working properly, ultimately causing a genetic disorder. Most carrier screens scan genes for mutations that cause autosomal recessive (AR) and X-linked disorders.

For most genes, everyone inherits two copies: one from mom and one from dad. A carrier is an individual who has one mutated copy and one normal copy of the same gene. Carriers typically do not have signs or symptoms of a genetic disorder.