Hemoglobinopathies

The Genetics of Hemoglobinopathies

Each person possesses two copies of the beta globin gene, on separate homologous chromosomes. In most people, the two copies are identical. A person with two identical gene copies is said to be homozygous.

In some people, the two beta copies are not identical. These people, who have two different alleles of the beta globin gene, are said to be heterozygous. The beta globin allele that leads to sickle cell disease is called the hemoglobin S (HbS) allele.

People who have inherited one HbA and one HbS allele are heterozygous for the beta chain gene. They are said to have the sickle cell trait, but not sickle cell disease. As long as they have one HbA allele, these individuals produce sufficient HbA to remain healthy, and they usually do not have any medical problems, or they experience only very mild symptoms. When both alleles must be abnormal to cause a disease, the condition is said to be recessive. Sickle cell disease is a recessive condition.

Sickle cell disease can occur when two individuals who have the sickle cell trait (they are called carriers) have children. Recall that the two beta chain alleles occur on different chromosomes. These homologous chromosomes separate during gamete formation, so that each gamete has a fifty-fifty chance of possessing an HbS allele. There is a one-in-four chance that a child conceived by two carriers will inherit a recessive, abnormal allele from each parent, and therefore be homozygous for the abnormal allele and develop sickle cell disease.

Homozygous forms of hemoglobinopathy can be very serious. Some cause so much damage that the fetus dies before birth, while others require lifelong treatment.