Genetic information provides the blueprint for the human body, and small variations in this code can have a range of effects on health. Some variations are inconsequential, while others may influence physical traits or disease susceptibility. One of the most common genetic changes worldwide is the alpha 3.7 deletion. This specific alteration affects the production of hemoglobin, the protein responsible for oxygen transport in the blood. Understanding this deletion is a starting point for grasping its potential health implications, which can vary from having no noticeable effect to contributing to a mild form of anemia.
The Genetics of Alpha-Globin and Thalassemia
Hemoglobin is the protein within red blood cells that binds to oxygen in the lungs and carries it to tissues throughout the body. A complete hemoglobin molecule is constructed from four protein chains: two alpha-globin chains and two beta-globin chains. The instructions for building the alpha-globin chains are encoded in two nearly identical genes, HBA1 and HBA2, located on chromosome 16. Most people inherit two copies of this chromosome, one from each parent, giving them a total of four alpha-globin genes.
When one or more of these genes are altered or missing, the production of alpha-globin is reduced. This imbalance leads to a group of genetic disorders known as alpha-thalassemia, with a severity that depends on how many genes are affected. The reduced alpha-globin disrupts the balance with beta-globin chains. This leads to an excess of beta-globin chains, which form unstable structures that damage red blood cells, causing their premature destruction and leading to anemia.
Defining the Alpha 3.7 Deletion
The name “alpha 3.7 deletion” refers to the size of the DNA segment missing from chromosome 16, which is 3,700 base pairs (3.7 kilobases). This deletion results from a genetic event called unequal crossing-over. During the production of sperm and egg cells, the two highly similar alpha-globin genes (HBA1 and HBA2) can misalign. This misalignment can cause a segment of DNA to be lost, removing one of the two genes.
This process results in a single, hybrid alpha-globin gene on the affected chromosome, often referred to as an -α3.7 allele. This remaining fusion gene is functional but produces alpha-globin protein at a lower rate than two separate, normal genes would. Consequently, a chromosome carrying the 3.7 deletion contributes less alpha-globin to the cell’s total pool.
Associated Health Conditions
The clinical impact of the alpha 3.7 deletion depends entirely on how many copies of the deletion an individual inherits. A person who inherits one chromosome with the deletion and one normal chromosome has a genotype of -α3.7/αα. This individual is known as a silent carrier. Silent carriers have three out of four functional alpha-globin genes and experience no symptoms, though some may exhibit a slight reduction in the average size of their red blood cells (microcytosis).
When an individual inherits two copies of the alpha 3.7 deletion, one from each parent, their genotype is -α3.7/-α3.7, a condition known as alpha-thalassemia trait. With only two functional alpha-globin genes, they experience a more noticeable reduction in hemoglobin production. This results in a mild microcytic anemia, where red blood cells are smaller and paler than usual. While often asymptomatic, some may report mild fatigue during physical exertion.
The health implications become more significant when the alpha 3.7 deletion is inherited alongside a more severe alpha-thalassemia mutation. Some mutations, like the Southeast Asian (–SEA) deletion, remove both alpha-globin genes from a single chromosome. An individual inheriting one chromosome with the –SEA deletion and the other with the -α3.7 deletion is left with only one functional alpha-globin gene. This genetic combination results in Hemoglobin H (HbH) disease.
HbH disease is characterized by a significant shortage of alpha-globin chains, which causes the formation of unstable Hemoglobin H. This damages red blood cells and leads to their rapid destruction. Individuals with HbH disease have moderate to severe anemia, an enlarged spleen (splenomegaly), and jaundice. They may require periodic blood transfusions, particularly during times of illness or physical stress, which can worsen the anemia.
Detection and Family Implications
The initial indication of an alpha-thalassemia condition often comes from a routine complete blood count (CBC). This test may reveal microcytosis and hypochromia, which describe red blood cells that are smaller and paler than normal. These findings can be the first clue for alpha-thalassemia trait. However, hemoglobin analysis can appear normal in silent carriers, making diagnosis with these methods alone difficult.
A definitive diagnosis of the alpha 3.7 deletion requires genetic testing. DNA-based tests, such as gap-polymerase chain reaction (gap-PCR), are designed to specifically identify the absence of the 3.7 kilobase DNA segment. This molecular confirmation is the most accurate way to distinguish alpha-thalassemia from other causes of microcytic anemia, such as iron deficiency.
The alpha 3.7 deletion is inherited in an autosomal recessive pattern, meaning a person must inherit a defective gene from both parents to have a more pronounced condition like alpha-thalassemia trait. Because carriers can be asymptomatic, they may be unaware they have the deletion. Genetic counseling is valuable for individuals identified with the deletion, especially when planning a family. If both partners are carriers of an alpha-thalassemia mutation, they have a 25% chance with each pregnancy of having a child with a more severe form, such as HbH disease.
Carrier screening is relevant in certain ethnic populations where the alpha 3.7 deletion is more common. This includes people of African, Mediterranean, Middle Eastern, and Asian descent. Identifying carriers allows for informed reproductive planning and can help prevent the birth of children with severe thalassemia syndromes like HbH disease or the fatal Hb Bart’s hydrops fetalis syndrome, which occurs when all four alpha-globin genes are absent.