Understanding Genetics
What are genes and why are they important?
Deoxyribonucleic acid (DNA) is made up of a combination of A, T, G, C base pairs, which code for the various genes in our body. There are over 20,000 genes in the human body which serve as the blueprint for bodily functions and processes. Changes (pathogenic variants previously known as mutations) in the DNA may alter the protein product, which can lead to disease. The most common gene variant involves a change or “misspelling” of the DNA code. Other variants 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 variant or gain an entirely new, but damaging, function.
Pathogenic Variants
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 their children. These harmful changes are called “pathogenic variants” and prevent the gene from working properly, ultimately causing a genetic disorder. Most carrier screens scan genes for pathogenic variants that cause autosomal recessive (AR) and X-linked disorders.
For most genes, everyone inherits two copies: one from their biological mother and one from their biological father. A carrier is an individual who has one gene with a pathogenic variant and one normal copy of the same gene. Carriers typically do not have signs or symptoms of a genetic disorder.
For most genes, everyone inherits two copies: one from their biological mother and one from their biological father. A carrier is an individual who has one gene with a pathogenic variant and one normal copy of the same gene. Carriers typically do not have signs or symptoms of a genetic disorder.
Inheritance Patterns
We have 46 chromosomes that come in pairs (23 pairs). One of each pair is inherited from your biological mother and the other from your biological father. The last set of chromosomes are called sex chromosomes and are paired as XX (typically female) or XY (typically male). There are five basic modes of inheritance for single-gene diseases: autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive, and mitochondrial.
Autosomal Dominant
Only one copy of a gene has a pathogenic variant 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 biological parent.
Autosomal Recessive
Both copies of a gene have a pathogenic variant for an individual to be affected with the genetic condition. Biological parents are usually unaffected but each “carry” a pathogenic variant in one of their two copies of the gene. If both biological 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 pathogenic variant is located on the X chromosome. Typically, individuals with one X chromosome are affected if they have the pathogenic variant on their X chromosome. Individuals with two X chromosomes with the pathogenic variant are typically unaffected because the additional X chromosome acts as a functioning backup copy, and are considered “carriers”. If an individual with two X chromosomes is a carrier for an X-linked condition, any XY offspring that they have has a 50% chance to be affected, and any XX offspring that they have has a 50% chance to be a carrier. If an individual with one X chromosome is affected, then ALL of their XY offspring will be neither affected nor carriers and ALL of their XX offspring will be carriers.
Rarely, XX individuals can inherit an X-linked recessive disorder. If both biological parents are affected, ALL of their offspring will be affected. If the XY parent is affected and the XX parent is a carrier, 50% of their offspring will be affected, while the other 50% will be unaffected individuals or carrier individuals.
Rarely, XX individuals can inherit an X-linked recessive disorder. If both biological parents are affected, ALL of their offspring will be affected. If the XY parent is affected and the XX parent is a carrier, 50% of their offspring will be affected, while the other 50% will be unaffected individuals or carrier individuals.
X-Linked Dominant
Similar to X-linked recessive, a pathogenic variant is located on the X chromosome. However, with X-linked dominant conditions, you only need one pathogenic variant to be affected. Both XX and XY individuals can be affected, although XY individuals may be more severely affected or may not survive. When an XX individual is affected, each pregnancy will have a 50% chance for offspring to inherit the X chromosome with the pathogenic variant. When an XY individual is affected, all their XX offspring will be affected, but none of their XY offspring will be affected.