Balanced Changes

A viewer from California to our web site ( sent the following question: “How is it possible that the DNA can mutate in ways that make one resistant to a disease? Like the AIDS virus. Would it be some sort of gene passed down from a generation through the next?”

This is an interesting question and a very real phenomenon. The term for what the viewer describes is heterozygous advantage and it is a situation in which some disease-causing genes are maintained in a population when the mutation is advantageous to that population. An example of this is sickle cell disease and resistance to malaria.

Sickle cell disease is an autosomal recessive disorder. In order to have the disease, the individual must inherit two doses of the disease-causing gene mutation, one from each parent. If you inherit only one dose, you are a carrier and have sickle cell trait. Individuals with only one copy of the altered gene are called heterozygotes. In sickle cell disease the gene affects hemoglobin, the oxygen-carrying protein in red blood cells. The disease affects millions worldwide and is the most common inherited blood disorder in the United States. It is estimated to occur in 1/500 African Americans and have a carrier frequency of 1/12 in that population. The carrier frequency refers to those individuals who carry one normal copy of the gene and one altered copy (heterozygote) but are unaffected.

Heterozygotes or carriers of certain recessive disorders exhibit a “heterozygous advantage” in that they can be resistant to certain infectious diseases. With sickle cell disease, the advantage of the heterozygote or carrier is resistance to malaria, a potential lethal parasitic infection that causes cycles of extreme chills and fevers. The malarial parasite’s entry into the human is through a bite from a female Anopheles mosquito which harbors the parasite in its salivary glands. The parasite gains entry into the red blood cells and is transported to the liver where the red blood cells eventually rupture, releasing parasites and causing subsequent infection. It is believed that the mechanism for the sickle cell carrier’s resistance is that the carrier’s red blood cells are relatively resistant to the parasite. The parasite cannot “take over” the red blood cells in the carrier like they can in someone who is not a carrier.

So to get back to the initial question: situations (sickle cell disease and others) do exist in nature where DNA changes or mutations have occurred that are beneficial to humans, providing resistance to certain diseases and these changes can be transmitted to subsequent generations. Not all gene changes are bad!

Thanks to Dr. Robert A. Saul

Study Participation

Eligible participants include individuals from birth to 60 years who have had genetic testing and have a documented molecular diagnosis of Angelman syndrome OR patients with a clear clinical diagnosis of Angelman syndrome who do not have a known molecular defect.

For more information, see the Angelman syndrome study fact sheet or contact This email address is being protected from spambots. You need JavaScript enabled to view it. , study coordinator.