Hemophilia is a genetic condition that impairs the body’s ability to form blood clots, leading to prolonged bleeding after an injury or, in severe cases, spontaneous internal bleeding. This disorder arises from a problem in the body’s instructions for making specific blood-clotting proteins. Hemophilia is caused by a gene mutation, which is a small-scale change in the DNA sequence, not a large-scale chromosome mutation. This specific alteration prevents the production of functional clotting proteins.
Understanding Gene Versus Chromosome Mutations
The distinction between a gene mutation and a chromosome mutation lies primarily in the scale of the genetic change. A gene mutation is a relatively small alteration that affects the DNA sequence of a single gene. These small-scale changes can involve a single nucleotide being substituted for another, or a few nucleotides being inserted or deleted from the sequence. Such changes modify the protein product, making it faulty or absent, as seen in conditions like hemophilia or cystic fibrosis.
A chromosome mutation is a large-scale structural or numerical change affecting entire chromosomes or significant segments of them. Chromosomes are the structures that package many genes together, so these mutations often involve hundreds or even thousands of genes at once. Examples include the deletion, duplication, or rearrangement of large chromosome pieces, or the gain or loss of a whole chromosome, such as in Down Syndrome.
Hemophilia falls into the gene mutation category because the underlying problem is highly specific. It is not a failure of a large piece of genetic material or an incorrect chromosome number that affects dozens of proteins. Instead, it is a targeted fault within the precise instructions for manufacturing a single clotting factor protein. This focuses the damage to one specific biochemical pathway.
The Specific Gene Responsible for Hemophilia
Hemophilia A and Hemophilia B are the most common forms of this bleeding disorder. They are caused by mutations in two different genes located on the X chromosome. Hemophilia A involves a mutation in the F8 gene, while Hemophilia B is linked to a mutation in the F9 gene. Both genes carry the instructions for making crucial blood-clotting proteins.
The F8 gene produces Factor VIII, and the F9 gene produces Factor IX. These proteins are known as clotting factors and are essential components in the complex cascade of chemical reactions that result in a stable blood clot. Without enough functional Factor VIII or Factor IX, the coagulation cascade breaks down, and a firm clot cannot be formed in response to injury.
The specific type of gene mutation can vary widely, ranging from minor single-nucleotide changes to large genetic rearrangements. For instance, in severe Hemophilia A, the most frequent cause is a large inversion—a segment of the F8 gene is flipped. Regardless of the exact type of mutation, the result is the same: the body produces an abnormal clotting factor, a reduced amount of the factor, or none at all.
How Hemophilia is Inherited
The location of the F8 and F9 genes on the X chromosome dictates the characteristic inheritance pattern of Hemophilia A and B. These conditions follow X-linked inheritance, meaning the mutated gene is carried on one of the two sex chromosomes. Females typically have two X chromosomes, while males have one X and one Y chromosome.
Because males possess only one X chromosome, they do not have a second copy of the gene to compensate if the first copy is faulty. If a male inherits an X chromosome with a mutated F8 or F9 gene, he will develop the disorder. This explains why hemophilia is far more common in males.
Females, having two X chromosomes, are typically protected because the normal gene on their second X chromosome can often produce enough functional clotting factor. A female with one mutated gene copy is known as a carrier. While she usually does not show severe symptoms, she can pass the mutation to her children. A son of a carrier mother has a 50% chance of inheriting the affected X chromosome and developing the disorder.